COVID-19-associated coagulopathy: Difference between revisions

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__NOTOC__
__NOTOC__
{{SI}}
{{SI}}
{{Main|COVID-19}}


{{CMG}}; {{AE}}
'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''


{{SK}}  
'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''
 
{{CMG}}; {{AE}} {{IF}}
 
{{SK}} Hematological findings and COVID-19, hypercoagulability in COVID-19, clotting disorder in COVID-19


==Overview==
==Overview==
[[Hypercoagulability]] is a major [[complication]] seen in as many as 31% of patients with [[COVID-19]]. It leads to many life-threatening outcomes, [[pulmonary embolism]] being the most common [[thrombotic]] complication. [[Hypercoagulability]] is characterized by elevated [[Fibrinogen]] and [[D-dimer]] levels. [[Coagulopathy]] in [[COVID-19]] must be differentiated from other diseases that cause disseminated intravascular coagulation ([[Disseminated intravascular coagulation|DIC]]). [[Prophylactic]] [[anticoagulation]] with [[low molecular weight heparin]] is given to all inpatients in the absence of active [[bleeding]]. Full dose [[anticoagulation]] is administered in patients with documented and confirmed [[venous thromboembolism]] ([[Venous thromboembolism|VTE]]) .


==Historical Perspective==
==Historical Perspective==
[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
There have been several outbreaks of [disease name], including -----.


In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
* The etiological agent is [[SARS-CoV-2]], named for the similarity of its symptoms to those induced by the [[severe acute respiratory syndrome]], causing [[coronavirus]] disease 2019 ([[COVID-19]]), is a [[virus]] identified as the cause of an outbreak of [[respiratory illness]] first detected in Wuhan, China.<ref name="LuCui2020">{{cite journal|last1=Lu|first1=Jian|last2=Cui|first2=Jie|last3=Qian|first3=Zhaohui|last4=Wang|first4=Yirong|last5=Zhang|first5=Hong|last6=Duan|first6=Yuange|last7=Wu|first7=Xinkai|last8=Yao|first8=Xinmin|last9=Song|first9=Yuhe|last10=Li|first10=Xiang|last11=Wu|first11=Changcheng|last12=Tang|first12=Xiaolu|title=On the origin and continuing evolution of SARS-CoV-2|journal=National Science Review|volume=7|issue=6|year=2020|pages=1012–1023|issn=2095-5138|doi=10.1093/nsr/nwaa036}}</ref>
*The rapidly increasing number of infected [[patients]] suggest that human-to-human transmission is actively occurring.
*The [[outbreak]] was declared a Public Health Emergency of International Concern on 30 January 2020.
*On March 12, 2020, the [[World Health Organization]] declared the [[COVID-19]] outbreak a [[pandemic]].


==Classification==
==Classification==
There is no established system for the classification of [disease name].
OR


[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].
* There is no established system for the classification of the [[hypercoagulability]] seen in [[COVID-19]].


OR
* The [[coagulopathy]] may be classified according to the type of vessels and organs involved into:<ref name="pmid324155792">{{cite journal| author=Becker RC| title=COVID-19 update: Covid-19-associated coagulopathy. | journal=J Thromb Thrombolysis | year= 2020 | volume= 50 | issue= 1 | pages= 54-67 | pmid=32415579 | doi=10.1007/s11239-020-02134-3 | pmc=7225095 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32415579  }}</ref>
**[[Venous thrombosis]]
**[[Arterial thrombosis]]
**[[Microvascular disease|Microvascular]] [[thrombosis]]


[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3].
* To view the classification of COVID-19, [[COVID-19 classification|click here]].
[Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].
 
OR
 
Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.
 
OR
 
If the staging system involves specific and characteristic findings and features:
According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].
 
OR
 
The staging of [malignancy name] is based on the [staging system].
 
OR
 
There is no established system for the staging of [malignancy name].


==Pathophysiology==
==Pathophysiology==
The exact pathogenesis of [disease name] is not fully understood.


OR
* [[COVID-19]] induces a [[Hypercoagulable state|hypercoagulable]] state in the body.  An increased risk of [[mortality]] has been noted in patient’s with [[coagulopathy]] in COVID-19. It is thought that the [[coagulopathy]] in COVID-19 is the result of:<ref name="pmid32415579" /><ref name="pmid320732132">{{cite journal| author=Tang N, Li D, Wang X, Sun Z| title=Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 4 | pages= 844-847 | pmid=32073213 | doi=10.1111/jth.14768 | pmc=7166509 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32073213  }}</ref>
 
**[[Virchow's triad|Virchow]]’s triad
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
** Vascular [[Endothelium|endothelial]] damage
 
**Endothelitis- direct invasion of endothelial cells by SARS-CoV-2 which exposes the [[vWF]] associated with a massive release of [[vWF]], eventually activating the [[coagulation cascade]].<ref name="pmid32305740">{{cite journal| author=Escher R, Breakey N, Lämmle B| title=Severe COVID-19 infection associated with endothelial activation. | journal=Thromb Res | year= 2020 | volume= 190 | issue=  | pages= 62 | pmid=32305740 | doi=10.1016/j.thromres.2020.04.014 | pmc=7156948 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32305740  }}</ref>
OR
**[[Complement system|Complement]] mediated damage to pericytes
 
**Pro-inflammatory [[Cytokine|cytokines]]- [[IL-1]], [[Interleukin 6|IL-6]], and [[TNF-α|TNF- α]], that activate the [[Coagulation cascade|coagulation]] pathway and the [[fibrinolytic]] system.<ref name="pmid32418715">{{cite journal| author=Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G| title=COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. | journal=Cytokine Growth Factor Rev | year= 2020 | volume= 53 | issue=  | pages= 66-70 | pmid=32418715 | doi=10.1016/j.cytogfr.2020.05.002 | pmc=7204669 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32418715  }}</ref><ref name="pmid7204669">{{cite journal| author=Luiten PG| title=Two visual pathways to the telencephalon in the nurse shark (Ginglymostoma cirratum). I. Retinal projections. | journal=J Comp Neurol | year= 1981 | volume= 196 | issue= 4 | pages= 531-8 | pmid=7204669 | doi=10.1002/cne.901960402 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7204669  }}</ref><ref name="pmid32513566">{{cite journal| author=Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L| title=SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. | journal=Cytokine Growth Factor Rev | year= 2020 | volume=  | issue=  | pages=  | pmid=32513566 | doi=10.1016/j.cytogfr.2020.06.001 | pmc=7265853 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32513566  }}</ref>
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*[[Stasis (medicine)|Stasis]]- Prolonged hospital admissions causing immobilization of the patient.
 
*[[Hypercoagulable state]]- Evidenced by elevated [[fibrinogen]], prothrombotic factors and [[Hyperviscosity syndrome|hyperviscosity]].<ref name="pmid32464112">{{cite journal| author=Maier CL, Truong AD, Auld SC, Polly DM, Tanksley CL, Duncan A| title=COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia? | journal=Lancet | year= 2020 | volume= 395 | issue= 10239 | pages= 1758-1759 | pmid=32464112 | doi=10.1016/S0140-6736(20)31209-5 | pmc=7247793 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32464112  }}</ref>
OR
*Some patients have been found to have [[Lupus anticoagulant]] ([[Anti-cardiolipin antibodies|anti-cardiolipin]]) and anti-β2GP1 [[antibodies]] that may be contributory.<ref name="pmid32369280">{{cite journal| author=Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP | display-authors=etal| title=Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. | journal=N Engl J Med | year= 2020 | volume= 383 | issue= 3 | pages= 288-290 | pmid=32369280 | doi=10.1056/NEJMc2013656 | pmc=7217555 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32369280  }}</ref>
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Causes==
==Causes==
Disease name] may be caused by [cause1], [cause2], or [cause3].
OR
Common causes of [disease] include [cause1], [cause2], and [cause3].


OR
* [[COVID-19|Coronavirus disease 2019 (COVID-19)]] is caused by a novel [[coronavirus]] called [[SARS-CoV-2]]  and is the cause of [[thrombocytopenia]] in [[COVID-19]] infection.


The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].
* To view causes of COVID-19, [[COVID-19 causes|click here]].


OR
==Differentiating COVID-19 associated coagulopathy from other Diseases==


The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click [[Pericarditis causes#Overview|here]].
* The main feature of COVID-19 coagulopathy is [[thrombosis]] while the acute phase of [[DIC]] presents with [[bleeding]].<ref name="pmid32407672">{{cite journal| author=Levi M, Thachil J, Iba T, Levy JH| title=Coagulation abnormalities and thrombosis in patients with COVID-19. | journal=Lancet Haematol | year= 2020 | volume= 7 | issue= 6 | pages= e438-e440 | pmid=32407672 | doi=10.1016/S2352-3026(20)30145-9 | pmc=7213964 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32407672  }}</ref>


==Differentiating ((Page name)) from other Diseases==
*Similar laboratory findings are: marked increase in [[D-dimer]] and normal/slightly low [[platelets]] and prolonged [[Prothrombin time|PT.]]
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
*Findings distinct in patients with COVID 19 are: high [[fibrinogen]] and high [[factor VIII]] activity
*The scoring system of the [https://www.isth.org/ International Society on Thrombosis and Hemostasis] should be used to detect DIC ([[platelet]] count, PT, [[fibrinogen]], D‐dimer, [[antithrombin]] and [[protein C]] activity monitoring), but the diagnosis and subsequent treatment should be done clinically.<ref name="pmid19222477">{{cite journal| author=Levi M, Toh CH, Thachil J, Watson HG| title=Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. | journal=Br J Haematol | year= 2009 | volume= 145 | issue= 1 | pages= 24-33 | pmid=19222477 | doi=10.1111/j.1365-2141.2009.07600.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19222477  }}</ref>


OR
* Coagulopathy in COVID-19 must also be differentiated from other diseases that cause [[Disseminated intravascular coagulation|DIC]] resulting in DVT and pulmonary embolism such as:
**[[Antithrombin III deficiency]]
** [[Factor V Leiden mutation]]
** [[Protein C deficiency]]
** [[Protein S deficiency]]
** [[Prothrombin gene mutation G20210A|Prothrombin gene mutation]]
** [[Antiphospholipid antibody syndrome]]


[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
For further information about the differential diagnosis, click [[COVID-19 associated coagulopathy differential diagnosis|here]].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.


OR
===Incidence===


In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
* The [[Incidence (epidemiology)|incidence]] of venous [[thromboembolism]] in [[Intensive care unit|ICU]] patients with COVID-19 was analyzed in a study by Klok et al.<ref name="pmid322910942">{{cite journal| author=Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM | display-authors=etal| title=Incidence of thrombotic complications in critically ill ICU patients with COVID-19. | journal=Thromb Res | year= 2020 | volume= 191 | issue=  | pages= 145-147 | pmid=32291094 | doi=10.1016/j.thromres.2020.04.013 | pmc=7146714 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32291094  }}</ref>


OR
* It concluded that the cumulative [[incidence]] of acute [[pulmonary embolism]] ([[Pulmonary embolism|PE]]), [[deep vein thrombosis]] ([[Deep vein thrombosis|DVT]]), [[ischemic stroke]], [[ST elevation myocardial infarction|MI]], or systemic [[Arterial embolism|arterial embolism was 31%.]]
* The [[Incidence (epidemiology)|incidence]] of most common [[Thrombosis|thrombotic]] complication was [[pulmonary embolism]] seen in 81% of patients. All these patients were on at least standard doses of thromboprophylaxis. <ref name="pmid32291094">{{cite journal| author=Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM | display-authors=etal| title=Incidence of thrombotic complications in critically ill ICU patients with COVID-19. | journal=Thromb Res | year= 2020 | volume= 191 | issue=  | pages= 145-147 | pmid=32291094 | doi=10.1016/j.thromres.2020.04.013 | pmc=7146714 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32291094  }} </ref><ref name="pmid7146714">{{cite journal| author=Woringer V, Renevey F| title=[A case of gonococcal arthritis at a young age]. | journal=Rev Med Suisse Romande | year= 1982 | volume= 102 | issue= 9 | pages= 863-5 | pmid=7146714 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7146714  }}</ref>
* The cumulative [[Incidence (epidemiology)|incidence]] of [[Venous thromboembolism|venous thromboembolism (VTE)]] were 16% (95% CI, 10-22) at 7 days, 33% (95% CI, 23-43) at 14 days and 42% (95% CI 30-54) at 21 days.
* Comparatively, the cumulative [[incidence]] of [[venous thromboembolism]] ([[Venous thromboembolism|VTE]]) was higher in the '''ICU''' patients - 26% (95% CI, 17-37) at 7 days, 47% (95% CI, 34-58) at 14 days and 59% (95% CI, 42-72) at 21 days) than on the floor.<ref name="pmid32369666">{{cite journal| author=Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA | display-authors=etal| title=Incidence of venous thromboembolism in hospitalized patients with COVID-19. | journal=J Thromb Haemost | year= 2020 | volume=  | issue=  | pages=  | pmid=32369666 | doi=10.1111/jth.14888 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32369666  }}</ref>


In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
To view the epidemiology and demographics for COVID-19, [[COVID-19 epidemiology and demographics|click here]].<br />


=== Age ===


* There is insufficient information regarding age-specific [[prevalence]] or incidence of [[COVID-19]]-associated [[coagulopathy]].


Patients of all age groups may develop [disease name].
=== Gender ===


OR
* There is insufficient information regarding gender-specific [[prevalence]] or incidence of [[COVID-19]]-associated [[coagulopathy]].


The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
=== Race ===


OR
* There is insufficient information regarding race-specific [[prevalence]] or incidence of [[COVID-19]]-associated [[coagulopathy]].


[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
==Risk Factors==
Common hypothesized [[Risk factor|risk factors]] for [[coagulopathy]] in [[COVID-19]] [[pneumonia]] based on studies include:<ref name="pmid32291094" /><ref name="WuChen2020">{{cite journal|last1=Wu|first1=Chaomin|last2=Chen|first2=Xiaoyan|last3=Cai|first3=Yanping|last4=Xia|first4=Jia’an|last5=Zhou|first5=Xing|last6=Xu|first6=Sha|last7=Huang|first7=Hanping|last8=Zhang|first8=Li|last9=Zhou|first9=Xia|last10=Du|first10=Chunling|last11=Zhang|first11=Yuye|last12=Song|first12=Juan|last13=Wang|first13=Sijiao|last14=Chao|first14=Yencheng|last15=Yang|first15=Zeyong|last16=Xu|first16=Jie|last17=Zhou|first17=Xin|last18=Chen|first18=Dechang|last19=Xiong|first19=Weining|last20=Xu|first20=Lei|last21=Zhou|first21=Feng|last22=Jiang|first22=Jinjun|last23=Bai|first23=Chunxue|last24=Zheng|first24=Junhua|last25=Song|first25=Yuanlin|title=Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China|journal=JAMA Internal Medicine|volume=180|issue=7|year=2020|pages=934|issn=2168-6106|doi=10.1001/jamainternmed.2020.0994}}</ref><ref name="urlManagement of Patients with Confirmed 2019-nCoV | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html |title=Management of Patients with Confirmed 2019-nCoV &#124; CDC |format= |work= |accessdate=}}</ref>


OR
*[[Intensive care unit|ICU]] admission
* Age (> 40 years)
*[[Hypoxia]]


[Chronic disease name] is usually first diagnosed among [age group].
Other general [[Risk factor|risk factors]] for [[venous thromboembolism]] ([[Venous thromboembolism|VTE]]) are:
* Male
* Active [[cancer]]
* Recent major [[surgery]]
* High [[Body mass index|BMI]] ([[obesity]])
* Prior [[Venous thromboembolism|VTE]]
* Immobilization
*[[Trauma]]


OR
To view the risk factors of COVID-19, [[COVID-19 risk factors|click here]].


[Acute disease name] commonly affects [age group].
==Screening==


* Every patient with [[COVID-19]] infection admitted to the hospital should have a baseline of basic blood investigations such as:<ref name="LevyConnors2020">{{cite journal|last1=Levy|first1=Jerrold H.|last2=Connors|first2=Jean M.|title=COVID-19 and its implications for thrombosis and anticoagulation|journal=Blood|volume=135|issue=23|year=2020|pages=2033–2040|issn=0006-4971|doi=10.1182/blood.2020006000}}</ref>
**[[Complete blood count]] ([[Complete blood count|CBC]])
**[[Platelet count]]
**[[Prothrombin time]] ([[Prothrombin time|PT]]), [[Activated partial thromboplastin time]] ([[Partial thromboplastin time|aPTT]])
**[[Fibrinogen]]
**[[D-dimer]]
**[[C-reactive protein]]


* Routine [[Screening (medicine)|screening]] with [[imaging]] is not done as there is no evidence to indicate an improvement in clinical outcomes.
* Depending on the clinical state of the patient and suspicion for the development of [[Venous thromboembolism|VTE]] or [[Artery|arterial]] thrombi, repeat testing and further imaging investigations are done.


There is no racial predilection to [disease name].
To view screening for COVID-19, [[COVID-19 screening|click here]].<br />


OR
==Natural History, Complications, and Prognosis==
 
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
 
 
 
[Disease name] affects men and women equally.


OR
===Natural History===


[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
* If left untreated, patients with [[coagulopathy]] may progress to develop [[Venous thromboembolism|VTE]], [[arterial thrombosis]], or microvascular [[thrombosis]] and ultimately succumb to death.


===Complications===
*[[Thrombosis|Thrombotic]] complications : <ref name="pmid32415579">{{cite journal| author=Becker RC| title=COVID-19 update: Covid-19-associated coagulopathy. | journal=J Thromb Thrombolysis | year= 2020 | volume=  | issue=  | pages=  | pmid=32415579 | doi=10.1007/s11239-020-02134-3 | pmc=7225095 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32415579  }} </ref><ref name="pmid32302462">{{cite journal| author=Barrett CD, Moore HB, Yaffe MB, Moore EE| title=ISTH interim guidance on recognition and management of coagulopathy in COVID-19: A comment. | journal=J Thromb Haemost | year= 2020 | volume=  | issue=  | pages=  | pmid=32302462 | doi=10.1111/jth.14860 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32302462  }}</ref>
**[[Deep vein thrombosis|Deep Vein Thrombosis]]
**[[Pulmonary embolism|Pulmonary Embolism]]
**[[Ischemic stroke]]
**[[Myocardial infarction]]
**[[Ischemia|Ischemic]] limbs
**Systemic arterial events
**Clotting of [[central venous catheter]]<nowiki/>s, [[dialysis]] catheter<nowiki/>s, and dialysis filters


=== Prognosis ===
[[Prognosis|Progn]][[Prognosis|osis]] depends on numerous factors:<ref name="pmid32306492">{{cite journal| author=Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z | display-authors=etal| title=D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 6 | pages= 1324-1329 | pmid=32306492 | doi=10.1111/jth.14859 | pmc=7264730 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32306492  }}</ref>
* Increased [[D-dimer]] levels- poor [[prognosis]]
* Increased  [[fibrin degradation product]] (FDP) levels <ref name="pmid32073213">{{cite journal| author=Tang N, Li D, Wang X, Sun Z| title=Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 4 | pages= 844-847 | pmid=32073213 | doi=10.1111/jth.14768 | pmc=7166509 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32073213  }} </ref>
*[[Intensive care unit|ICU]] admission


The majority of [disease name] cases are reported in [geographical region].
Independent predictors of thrombotic complications include:


OR


[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].


==Risk Factors==
*[[Age]]
There are no established risk factors for [disease name].
*[[Coagulopathy]] (defined as spo<nowiki/>ntaneou<nowiki/>s prolongatio<nowiki/>n of th<nowiki/>e [[prothrombin time]] > 3 s or [[activated partial thromboplastin time]] > 5 s)
*Active [[cancer]]


OR
To view natural history, complications, and prognosis of [[COVID-19]], [[COVID-19 natural history, complications, and prognosis|click here]].
 
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
 
OR
 
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
 
OR
 
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
 
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].
 
OR
 
According to the [guideline name], screening for [disease name] is not recommended.
 
OR
 
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
 
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
 
OR
 
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
 
OR
 
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Study of Choice===
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].


OR
*The diagnosis of [[coagulopathy]] in [[COVID-19]] is based mainly on the laboratory findings showing a pro-coagulant profile.
*The pre-test probability of [[DVT]] and [[PE]] can be calculated using the [[Wells Score|Wells' criteria]]
*[[Computed tomography]] with [[pulmonary angiography]] ([[CT pulmonary angiogram|CTPA]]) is the diagnostic test of choice. [[Ventilation/perfusion scan|Ventilation/Perfusion]] scan may also be done, but may not be of much yield in patients with [[COVID-19]].
*To view the study of choice for diagnosis of [[COVID-19]], [[COVID-19 diagnostic study of choice|click here]].<br />


The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
===History and Symptoms===
The [[symptoms]] depend on the vessels and the organ systems involved.  


OR
'''Pulmonary Embolism:''' Many symptoms of [[Pulmonary embolism|PE]] overlap with the [[respiratory]] symptoms seen in [[COVID-19]].
* Maybe [[asymptomatic]]
* [[Dyspnea]]
* [[Chest pain]]
* [[Cough]]
* Some other rare presentations include- [[hemoptysis]], [[shock]], [[hypotension]], death.


The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
A positive history of the following is suggestive of and contributory:
* Immobilization or prolonged [[hospitalization]]
* Recent [[surgery]]
*[[Trauma]]
*[[Obesity]]
* History of previous venous [[thromboembolism]] ([[Venous thromboembolism|VTE]])
*[[Malignancy]]
* Stroke with [[hemiplegia]] or [[immobility]]
* Age >65 years


OR
'''Deep Vein Thrombosis'''
* [[Swelling]]
* [[Edema]]
* [[Pain]]
* Warmth


There are no established criteria for the diagnosis of [disease name].
[[Arterial thrombosis]] involving various systems show the following symptoms:
* '''Ischemic Stroke:''' Various focal [[neurological]] deficits depending on the large artery involved
* '''Myocardial infarction:''' [[Chest pain]] radiating to left arm and neck, sweating, [[dyspnea]]
* '''Acute ischemic limb:''' Pain, pallor, [[poikilothermia]], [[pulselessness]], [[paresthesia]], [[paralysis]]


===History and Symptoms===
To view the history and symptoms of COVID-19, [[COVID-19 history and symptoms|click here]].
The majority of patients with [disease name] are asymptomatic.
 
OR
 
The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].


===Physical Examination===
===Physical Examination===
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].


OR
'''Pulmonary Embolism'''


Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
Physical examination of patients with [[Pulmonary embolism|Pulmonary Embolism]] is usually remarkable for:
*[[Tachycardia]]
*[[Tachypnea]]
*[[Diaphoresis]]


OR
'''Deep Vein Thrombosis'''


The presence of [finding(s)] on physical examination is diagnostic of [disease name].
Physical examination of patients with [[Deep Vein Thrombosis]] includes:
* Unilateral swelling/[[edema]] with a difference in diameters
* [[Warmth]]
* [[Tenderness]]
* Dilated [[veins]]
* [[Homan's sign]] may also be seen but is unreliable.


OR
[[Arterial]] [[thrombosis]]:
 
* '''Ischemic Stroke:''' Focal neurological deficits depending on the vessel involved
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
* '''Myocardial Infarction:''' Uncomfortable appearing patient with [[diaphoresis]]
* '''Ischemic Limb:''' Pallor, [[poikilothermia]], [[pulselessness]], [[paresthesia]], [[paralysis]]
To view the complete physical examination in [[COVID-19]], [[COVID-19 physical examination|click here]].


===Laboratory Findings===
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
* An elevated concentration of serum/blood pro-coagulant factors is diagnostic of [[coagulopathy]] associated with [[COVID-19]].
 
* Laboratory findings consistent with the diagnosis of [[COVID-19]] associated [[coagulopathy]] include:<ref name="pmid2302448">{{cite journal| author=Wasserbauer R, Beranová M, Vancurová D, Dolezel B| title=Biodegradation of polyethylene foils by bacterial and liver homogenates. | journal=Biomaterials | year= 1990 | volume= 11 | issue= 1 | pages= 36-40 | pmid=2302448 | doi=10.1016/0142-9612(90)90049-v | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2302448  }}</ref><ref name="pmid32302448">{{cite journal| author=Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M | display-authors=etal| title=The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 7 | pages= 1747-1751 | pmid=32302448 | doi=10.1111/jth.14854 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32302448  }}</ref>
OR
**[[Coagulation]] testing- pro-coagulant profile which includes:
 
***[[Platelet]] Counts- Normal or increased
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
***[[Prothrombin time]] (PT) and [[activated partial thromboplastin time]] ([[aPTT]])-  normal or slightly prolonged
 
***[[Fibrinogen]]- increased
OR
***[[D-dimer]]- increased
 
***[[Factor VIII]] activity- increased
[Test] is usually normal among patients with [disease name].
***[[Von Willebrand factor|VWF]] antigen- increased
 
***[[Protein C]], [[Protein S]], [[Antithrombin III]] - slightly decreased
OR
* [[TEGT|TEG]] findings:<ref name="pmid32302438">{{cite journal| author=Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V | display-authors=etal| title=Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 7 | pages= 1738-1742 | pmid=32302438 | doi=10.1111/jth.14850 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32302438  }}</ref><ref name="pmid323024482">{{cite journal| author=Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M | display-authors=etal| title=The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 7 | pages= 1747-1751 | pmid=32302448 | doi=10.1111/jth.14854 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32302448  }}</ref>
 
** Reaction time (R) - decreased
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
**[[Clot]] formation time (K)- decreased
 
** Maximum amplitude (MA)- increased
OR
** Clot lysis at 30 minutes (LY30)-  decreased
 
To view the laboratory findings on COVID-19, [[COVID-19 laboratory findings|click here]].
There are no diagnostic laboratory findings associated with [disease name].
 
===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].
An [[The electrocardiogram|ECG]] may be helpful in the diagnosis of [[pulmonary embolism]] or [[myocardial infarction]] caused due to hypercoagulability in [[COVID-19]].
 
*Findings on an [[The electrocardiogram|ECG]] suggestive of/diagnostic of [[pulmonary embolism]] include tachycardia and S1Q3T3 pattern.
OR
*Findings on an [[The electrocardiogram|ECG]] suggestive of/diagnostic of [[myocardial infarction]] include STE elevation in various leads.
 
*To view the electrocardiogram findings on COVID-19, [[COVID-19 electrocardiogram|click here]].<br />
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
===X-ray===
===X-ray===
There are no x-ray findings associated with [disease name].
* There are no specific x-ray findings associated with [[PE]].  
 
* However, an x-ray may be helpful in ruling out other causes with similar symptoms like [[pneumonia]], [[cardiogenic]] causes of [[dyspnea]], and [[pneumothorax]].
OR
*To view the x-ray finidings on COVID-19, [[COVID-19 x ray|click here]].<br />
 
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound  findings associated with [disease name].
*[[Echocardiography]] may be helpful in the diagnosis of [[pulmonary embolism]].
 
*[[Ultrasound|Compressive Ultrasound]] may be helpful in the diagnosis of [[deep vein thrombosis]]
OR
*To view the echocardiographic findings on COVID-19, [[COVID-19 echocardiography and ultrasound|click here]].<br />
 
Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===CT scan===
===CT scan===
There are no CT scan findings associated with [disease name].
===== CTPA and Ventilation Perfusion(V/Q) Scan =====
 
*Prompt diagnosis of PE in COVID-19 patient is difficult in this regard that various symptoms of [[COVID-19]] overlap with that of [[pulmonary embolism]]. American Society of Hematology provides the following guidelines regarding the diagnosis of pulmonary embolism:<ref name="pmid32383092">{{cite journal| author=Lu Y, Macapinlac HA| title=Perfusion SPECT/CT to diagnose pulmonary embolism during COVID-19 pandemic. | journal=Eur J Nucl Med Mol Imaging | year= 2020 | volume= 47 | issue= 9 | pages= 2064-2065 | pmid=32383092 | doi=10.1007/s00259-020-04851-6 | pmc=7205478 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32383092  }}</ref>
OR
** Normal [[d-dimers]] level in a patient with low to moderate [[Pretest probability of DVT|pretest probability]] is sufficient to rule out the diagnosis of PE. [[D-dimers|D-dimers level]] is usually elevated in COVID-19 patients. This is not applicable to a patient with a high pretest probability.
 
** Inpatient with suspected PE with symptoms like [[hypotension]], [[tachycardia]], and sudden drop in [[oxygen saturation]] with a high pretest probability of PE, computed [[tomography]] with [[pulmonary angiography]] is used for the diagnosis. Contraindication to the use of [[CT pulmonary angiogram|CTPA]] warrants investigation with [[Ventilation/perfusion scan|ventilation/perfusion scan.]]
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


OR
[[File:Covid-19-pneumonia-and-pulmonary-emboli.jpg|thumb|800x800px| '''Right-sided segmental and subsegmental pulmonary arterial filling defects (yellow arrows) in keeping with acute distal pulmonary emboli.''' Case courtesy of Dr Gianluca Martinelli, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/76817">rID: 76817</a> |center]]


There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
To view the [[Computed tomography|CT]] scan findings on [[COVID-19]], [[COVID-19 CT scan|click here]].


===MRI===
===MRI===
There are no MRI findings associated with [disease name].
*There are no [[Magnetic resonance imaging|MRI]] findings associated with [[coagulopathy]] of [[COVID-19]] unless it is used to diagnose and evaluate an [[ischemic stroke]] caused by it.
 
*To view the [[Magnetic resonance imaging|MRI]] findings on [[COVID-19|COVID-19,]] [[COVID-19 MRI|click here]].<br />
OR
 
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
There are no other imaging findings associated with [[coagulopathy]] of [[COVID-19]].
 
OR
 
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


===Other Diagnostic Studies===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
* To view other diagnostic studies for [[COVID-19]], [[COVID-19 other diagnostic studies|click here]].<br />
 
OR
 
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
'''Prophylactic dose of anticoagulation'''
 
* Drug- [[Low-molecular-weight heparin]] ([[Low molecular weight heparin|LMWH]]) is preferred over [[unfractionated heparin]] to reduce contact with the patient.
OR
*[[Unfractionated heparin]] may be used in case of unavailability or severe [[Renal insufficiency|renal impairment]].
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.
 
OR
 
[Disease name] is a medical emergency and requires prompt treatment.
 
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR


[Therapy] is recommended among all patients who develop [disease name].
Indications:
* All inpatients in the absence of active [[bleeding]]
* To be held only if [[Platelet|platelet counts]] fall below 25 x 109/L, or [[fibrinogen]] less than 0.5 g/L
* In case of a history of [[heparin-induced thrombocytopenia]](HIT), [[fondaparinux]] is used.


OR
'''Intermediate or therapeutic dose anticoagulation'''
* Preferred regimen: [[Enoxaparin]] 40 to 60 mg once daily<ref name="pmid322201122">{{cite journal| author=Tang N, Bai H, Chen X, Gong J, Li D, Sun Z| title=Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 5 | pages= 1094-1099 | pmid=32220112 | doi=10.1111/jth.14817 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32220112  }}</ref>


Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
Indications:
*Critically ill patients or [[Intensive care unit|ICU]] patients<ref name="pmid323024422">{{cite journal| author=Akima S, McLintock C, Hunt BJ| title=RE: ISTH interim guidance to recognition and management of coagulopathy in COVID-19. | journal=J Thromb Haemost | year= 2020 | volume=  | issue=  | pages=  | pmid=32302442 | doi=10.1111/jth.14853 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32302442  }}</ref>
* According to a study, a better [[prognosis]] was seen in patients who met the SIC ([[Sepsis]]-induced [[coagulopathy]]) criteria or had marked elevated [[D-dimer]] levels and were put on anticoagulant therapy(mainly with [[low molecular weight heparin]]) <ref name="pmid32220112">{{cite journal| author=Tang N, Bai H, Chen X, Gong J, Li D, Sun Z| title=Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 5 | pages= 1094-1099 | pmid=32220112 | doi=10.1111/jth.14817 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32220112  }} </ref>


OR
'''Therapeutic/ full-dose anticoagulation'''
* Preferred regimen: [[Enoxaparin]] 1 mg/kg every 12 hours


Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
Indications:
* Suspected [[Venous thromboembolism|VTE]]/[[Pulmonary embolism|PE]]
* Confirmed [[Venous thromboembolism|VTE]]/[[Pulmonary embolism|PE]]
* Clotting in [[Catheter|catheters]], or [[extracorporeal]] circuits like [[Extracorporeal membrane oxygenation|ECMO]] and CRRT. <ref name="pmid32302442">{{cite journal| author=Akima S, McLintock C, Hunt BJ| title=RE: ISTH interim guidance to recognition and management of coagulopathy in COVID-19. | journal=J Thromb Haemost | year= 2020 | volume=  | issue=  | pages=  | pmid=32302442 | doi=10.1111/jth.14853 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32302442  }} </ref>


OR
'''Post-discharge thromboprophylaxis'''
* Drug and dose-  Regulatory-approved regimen<ref name="pmid27232649">{{cite journal| author=Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A | display-authors=etal| title=Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. | journal=N Engl J Med | year= 2016 | volume= 375 | issue= 6 | pages= 534-44 | pmid=27232649 | doi=10.1056/NEJMoa1601747 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27232649  }}</ref>
**Preferred regimen (1): [[Betrixaban]] 160 mg on day 1, followed by 80 mg once daily for 35-42 days
**Preferred regimen (2): [[Rivaroxaban]] 10 mg daily for 31-39 days


Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
Indications:
* Patients with documented venous thromboembolism [[Venous thromboembolism|(VTE]]) require thromboprophylaxis for up to 90 days after discharge.
* Some patients who do not have [[Venous thromboembolism|VTE]] but require extended thromboprophylaxis include:
**Acute medical illness, older age, immobilization, recent surgery, or trauma.
*Most of these criteria are met by patients with COVID-19, and they require thromboprophylaxis for up to 90 days after discharge.<ref name="pmid32311448">{{cite journal| author=Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E | display-authors=etal| title=COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. | journal=J Am Coll Cardiol | year= 2020 | volume= 75 | issue= 23 | pages= 2950-2973 | pmid=32311448 | doi=10.1016/j.jacc.2020.04.031 | pmc=7164881 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32311448  }}</ref>


OR
'''Bleeding in COVID-19'''
*[[Transfusion]] and replacement; discontinuation or reversal of [[Anticoagulant|anticoagulation]] are the mainstay of treatment
* Transfuse [[Platelet|platelets]]  if the platelet count is less than 50 x 109/L
* Administer [[Blood plasma|plasma]] if the [[INR]] is above 1.8
* Order [[fibrinogen]] concentrate or [[cryoprecipitate]] if the [[fibrinogen]] level is less than 1.5 g/L


Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
*To view medical treatment for COVID-19, click here.


===Surgery===
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
Surgical intervention is not recommended for the management of COVID-19 associated coagulopathy.
 
OR
 
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
 
OR
 
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
 
OR
 
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
 
OR
 
Surgery is the mainstay of treatment for [disease or malignancy].


===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
OR
There are no available vaccines against [disease name].


OR
* Since there is no vaccine for COVID-19 there are plenty of primary prevention suggested from CDC such as:<ref>{{Cite web|url=https://www.cdc.gov/coronavirus/2019-ncov/index.html|title=|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
** Hand washing every 10 minutes.
** Using alcoholic hand sanitizer.
** Self [[quarantine]] for two weeks if [[symptomatic]].


Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
* To view the primary prevention measures of COVID-19, click [[COVID-19 primary prevention|here]].
 
OR
 
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].


===Secondary Prevention===
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].


OR
*[[World Health Organization|WHO]] recommends home care for patients with suspected [[COVID-19]] who present with mild symptoms:<ref>{{cite web |url=https://www.who.int/publications/i/item/home-care-for-patients-with-suspected-novel-coronavirus-(ncov)-infection-presenting-with-mild-symptoms-and-management-of-contacts |title=Home care for patients with COVID-19 presenting with mild symptoms and management of their contacts |format= |work= |accessdate=}}</ref>
 
**Family members of an infected patient are better to wear masks.
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
**Using separate bathroom and bedroom by the infected person.
**Using [[antipyretics]] and analgesics for [[fever]], [[myalgias]], and [[headaches]]
* To view the secondary prevention measures of COVID-19, click [[COVID-19 secondary prevention|here]].
[[File:Patho covid anticoagulation.jpg|600px|center]]


==References==
==References==
{{reflist|2}}
{{reflist|2}}
 
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Main article: COVID-19

For COVID-19 frequently asked inpatient questions, click here

For COVID-19 frequently asked outpatient questions, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ifrah Fatima, M.B.B.S[2]

Synonyms and keywords: Hematological findings and COVID-19, hypercoagulability in COVID-19, clotting disorder in COVID-19

Overview

Hypercoagulability is a major complication seen in as many as 31% of patients with COVID-19. It leads to many life-threatening outcomes, pulmonary embolism being the most common thrombotic complication. Hypercoagulability is characterized by elevated Fibrinogen and D-dimer levels. Coagulopathy in COVID-19 must be differentiated from other diseases that cause disseminated intravascular coagulation (DIC). Prophylactic anticoagulation with low molecular weight heparin is given to all inpatients in the absence of active bleeding. Full dose anticoagulation is administered in patients with documented and confirmed venous thromboembolism (VTE) .

Historical Perspective

Classification

  • To view the classification of COVID-19, click here.

Pathophysiology

Causes

Differentiating COVID-19 associated coagulopathy from other Diseases

For further information about the differential diagnosis, click here.

Epidemiology and Demographics

Incidence

To view the epidemiology and demographics for COVID-19, click here.

Age

Gender

Race

Risk Factors

Common hypothesized risk factors for coagulopathy in COVID-19 pneumonia based on studies include:[14][17][18]

Other general risk factors for venous thromboembolism (VTE) are:

To view the risk factors of COVID-19, click here.

Screening

  • Routine screening with imaging is not done as there is no evidence to indicate an improvement in clinical outcomes.
  • Depending on the clinical state of the patient and suspicion for the development of VTE or arterial thrombi, repeat testing and further imaging investigations are done.

To view screening for COVID-19, click here.

Natural History, Complications, and Prognosis

Natural History

Complications

Prognosis

Prognosis depends on numerous factors:[21]

Independent predictors of thrombotic complications include:


To view natural history, complications, and prognosis of COVID-19, click here.

Diagnosis

Diagnostic Study of Choice

History and Symptoms

The symptoms depend on the vessels and the organ systems involved.

Pulmonary Embolism: Many symptoms of PE overlap with the respiratory symptoms seen in COVID-19.

A positive history of the following is suggestive of and contributory:

Deep Vein Thrombosis

Arterial thrombosis involving various systems show the following symptoms:

To view the history and symptoms of COVID-19, click here.

Physical Examination

Pulmonary Embolism

Physical examination of patients with Pulmonary Embolism is usually remarkable for:

Deep Vein Thrombosis

Physical examination of patients with Deep Vein Thrombosis includes:

Arterial thrombosis:

To view the complete physical examination in COVID-19, click here.

Laboratory Findings

To view the laboratory findings on COVID-19, click here.

Electrocardiogram

An ECG may be helpful in the diagnosis of pulmonary embolism or myocardial infarction caused due to hypercoagulability in COVID-19.

  • Findings on an ECG suggestive of/diagnostic of pulmonary embolism include tachycardia and S1Q3T3 pattern.
  • Findings on an ECG suggestive of/diagnostic of myocardial infarction include STE elevation in various leads.
  • To view the electrocardiogram findings on COVID-19, click here.

X-ray

  • There are no specific x-ray findings associated with PE.
  • However, an x-ray may be helpful in ruling out other causes with similar symptoms like pneumonia, cardiogenic causes of dyspnea, and pneumothorax.
  • To view the x-ray finidings on COVID-19, click here.

Echocardiography or Ultrasound

CT scan

CTPA and Ventilation Perfusion(V/Q) Scan
Right-sided segmental and subsegmental pulmonary arterial filling defects (yellow arrows) in keeping with acute distal pulmonary emboli. Case courtesy of Dr Gianluca Martinelli, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/76817">rID: 76817</a>

To view the CT scan findings on COVID-19, click here.

MRI

Other Imaging Findings

There are no other imaging findings associated with coagulopathy of COVID-19.

Other Diagnostic Studies

Treatment

Medical Therapy

Prophylactic dose of anticoagulation

Indications:

Intermediate or therapeutic dose anticoagulation

Indications:

Therapeutic/ full-dose anticoagulation

  • Preferred regimen: Enoxaparin 1 mg/kg every 12 hours

Indications:

Post-discharge thromboprophylaxis

  • Drug and dose- Regulatory-approved regimen[32]
    • Preferred regimen (1): Betrixaban 160 mg on day 1, followed by 80 mg once daily for 35-42 days
    • Preferred regimen (2): Rivaroxaban 10 mg daily for 31-39 days

Indications:

  • Patients with documented venous thromboembolism (VTE) require thromboprophylaxis for up to 90 days after discharge.
  • Some patients who do not have VTE but require extended thromboprophylaxis include:
    • Acute medical illness, older age, immobilization, recent surgery, or trauma.
  • Most of these criteria are met by patients with COVID-19, and they require thromboprophylaxis for up to 90 days after discharge.[33]

Bleeding in COVID-19

  • To view medical treatment for COVID-19, click here.

Surgery

Surgical intervention is not recommended for the management of COVID-19 associated coagulopathy.

Primary Prevention

  • Since there is no vaccine for COVID-19 there are plenty of primary prevention suggested from CDC such as:[34]
    • Hand washing every 10 minutes.
    • Using alcoholic hand sanitizer.
    • Self quarantine for two weeks if symptomatic.
  • To view the primary prevention measures of COVID-19, click here.

Secondary Prevention

  • WHO recommends home care for patients with suspected COVID-19 who present with mild symptoms:[35]
    • Family members of an infected patient are better to wear masks.
    • Using separate bathroom and bedroom by the infected person.
    • Using antipyretics and analgesics for fever, myalgias, and headaches
  • To view the secondary prevention measures of COVID-19, click here.

References

  1. ↑ Lu, Jian; Cui, Jie; Qian, Zhaohui; Wang, Yirong; Zhang, Hong; Duan, Yuange; Wu, Xinkai; Yao, Xinmin; Song, Yuhe; Li, Xiang; Wu, Changcheng; Tang, Xiaolu (2020). "On the origin and continuing evolution of SARS-CoV-2". National Science Review. 7 (6): 1012–1023. doi:10.1093/nsr/nwaa036. ISSN 2095-5138.
  2. ↑ Becker RC (2020). "COVID-19 update: Covid-19-associated coagulopathy". J Thromb Thrombolysis. 50 (1): 54–67. doi:10.1007/s11239-020-02134-3. PMC 7225095 Check |pmc= value (help). PMID 32415579 Check |pmid= value (help).
  3. ↑ 3.0 3.1 Becker RC (2020). "COVID-19 update: Covid-19-associated coagulopathy". J Thromb Thrombolysis. doi:10.1007/s11239-020-02134-3. PMC 7225095 Check |pmc= value (help). PMID 32415579 Check |pmid= value (help).
  4. ↑ Tang N, Li D, Wang X, Sun Z (2020). "Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia". J Thromb Haemost. 18 (4): 844–847. doi:10.1111/jth.14768. PMC 7166509 Check |pmc= value (help). PMID 32073213 Check |pmid= value (help).
  5. ↑ Escher R, Breakey N, Lämmle B (2020). "Severe COVID-19 infection associated with endothelial activation". Thromb Res. 190: 62. doi:10.1016/j.thromres.2020.04.014. PMC 7156948 Check |pmc= value (help). PMID 32305740 Check |pmid= value (help).
  6. ↑ Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G (2020). "COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons". Cytokine Growth Factor Rev. 53: 66–70. doi:10.1016/j.cytogfr.2020.05.002. PMC 7204669 Check |pmc= value (help). PMID 32418715 Check |pmid= value (help).
  7. ↑ Luiten PG (1981). "Two visual pathways to the telencephalon in the nurse shark (Ginglymostoma cirratum). I. Retinal projections". J Comp Neurol. 196 (4): 531–8. doi:10.1002/cne.901960402. PMID 7204669.
  8. ↑ Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L (2020). "SARS-CoV-2 infection: The role of cytokines in COVID-19 disease". Cytokine Growth Factor Rev. doi:10.1016/j.cytogfr.2020.06.001. PMC 7265853 Check |pmc= value (help). PMID 32513566 Check |pmid= value (help).
  9. ↑ Maier CL, Truong AD, Auld SC, Polly DM, Tanksley CL, Duncan A (2020). "COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?". Lancet. 395 (10239): 1758–1759. doi:10.1016/S0140-6736(20)31209-5. PMC 7247793 Check |pmc= value (help). PMID 32464112 Check |pmid= value (help).
  10. ↑ Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP; et al. (2020). "Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19". N Engl J Med. 383 (3): 288–290. doi:10.1056/NEJMc2013656. PMC 7217555 Check |pmc= value (help). PMID 32369280 Check |pmid= value (help).
  11. ↑ Levi M, Thachil J, Iba T, Levy JH (2020). "Coagulation abnormalities and thrombosis in patients with COVID-19". Lancet Haematol. 7 (6): e438–e440. doi:10.1016/S2352-3026(20)30145-9. PMC 7213964 Check |pmc= value (help). PMID 32407672 Check |pmid= value (help).
  12. ↑ Levi M, Toh CH, Thachil J, Watson HG (2009). "Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology". Br J Haematol. 145 (1): 24–33. doi:10.1111/j.1365-2141.2009.07600.x. PMID 19222477.
  13. ↑ Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM; et al. (2020). "Incidence of thrombotic complications in critically ill ICU patients with COVID-19". Thromb Res. 191: 145–147. doi:10.1016/j.thromres.2020.04.013. PMC 7146714 Check |pmc= value (help). PMID 32291094 Check |pmid= value (help).
  14. ↑ 14.0 14.1 Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM; et al. (2020). "Incidence of thrombotic complications in critically ill ICU patients with COVID-19". Thromb Res. 191: 145–147. doi:10.1016/j.thromres.2020.04.013. PMC 7146714 Check |pmc= value (help). PMID 32291094 Check |pmid= value (help).
  15. ↑ Woringer V, Renevey F (1982). "[A case of gonococcal arthritis at a young age]". Rev Med Suisse Romande. 102 (9): 863–5. PMID 7146714.
  16. ↑ Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA; et al. (2020). "Incidence of venous thromboembolism in hospitalized patients with COVID-19". J Thromb Haemost. doi:10.1111/jth.14888. PMID 32369666 Check |pmid= value (help).
  17. ↑ Wu, Chaomin; Chen, Xiaoyan; Cai, Yanping; Xia, Jia’an; Zhou, Xing; Xu, Sha; Huang, Hanping; Zhang, Li; Zhou, Xia; Du, Chunling; Zhang, Yuye; Song, Juan; Wang, Sijiao; Chao, Yencheng; Yang, Zeyong; Xu, Jie; Zhou, Xin; Chen, Dechang; Xiong, Weining; Xu, Lei; Zhou, Feng; Jiang, Jinjun; Bai, Chunxue; Zheng, Junhua; Song, Yuanlin (2020). "Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China". JAMA Internal Medicine. 180 (7): 934. doi:10.1001/jamainternmed.2020.0994. ISSN 2168-6106.
  18. ↑ "Management of Patients with Confirmed 2019-nCoV | CDC".
  19. ↑ Levy, Jerrold H.; Connors, Jean M. (2020). "COVID-19 and its implications for thrombosis and anticoagulation". Blood. 135 (23): 2033–2040. doi:10.1182/blood.2020006000. ISSN 0006-4971.
  20. ↑ Barrett CD, Moore HB, Yaffe MB, Moore EE (2020). "ISTH interim guidance on recognition and management of coagulopathy in COVID-19: A comment". J Thromb Haemost. doi:10.1111/jth.14860. PMID 32302462 Check |pmid= value (help).
  21. ↑ Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z; et al. (2020). "D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19". J Thromb Haemost. 18 (6): 1324–1329. doi:10.1111/jth.14859. PMC 7264730 Check |pmc= value (help). PMID 32306492 Check |pmid= value (help).
  22. ↑ Tang N, Li D, Wang X, Sun Z (2020). "Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia". J Thromb Haemost. 18 (4): 844–847. doi:10.1111/jth.14768. PMC 7166509 Check |pmc= value (help). PMID 32073213 Check |pmid= value (help).
  23. ↑ Wasserbauer R, Beranová M, Vancurová D, Dolezel B (1990). "Biodegradation of polyethylene foils by bacterial and liver homogenates". Biomaterials. 11 (1): 36–40. doi:10.1016/0142-9612(90)90049-v. PMID 2302448.
  24. ↑ Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M; et al. (2020). "The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome". J Thromb Haemost. 18 (7): 1747–1751. doi:10.1111/jth.14854. PMID 32302448 Check |pmid= value (help).
  25. ↑ Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V; et al. (2020). "Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis". J Thromb Haemost. 18 (7): 1738–1742. doi:10.1111/jth.14850. PMID 32302438 Check |pmid= value (help).
  26. ↑ Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M; et al. (2020). "The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome". J Thromb Haemost. 18 (7): 1747–1751. doi:10.1111/jth.14854. PMID 32302448 Check |pmid= value (help).
  27. ↑ Lu Y, Macapinlac HA (2020). "Perfusion SPECT/CT to diagnose pulmonary embolism during COVID-19 pandemic". Eur J Nucl Med Mol Imaging. 47 (9): 2064–2065. doi:10.1007/s00259-020-04851-6. PMC 7205478 Check |pmc= value (help). PMID 32383092 Check |pmid= value (help).
  28. ↑ Tang N, Bai H, Chen X, Gong J, Li D, Sun Z (2020). "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy". J Thromb Haemost. 18 (5): 1094–1099. doi:10.1111/jth.14817. PMID 32220112 Check |pmid= value (help).
  29. ↑ Akima S, McLintock C, Hunt BJ (2020). "RE: ISTH interim guidance to recognition and management of coagulopathy in COVID-19". J Thromb Haemost. doi:10.1111/jth.14853. PMID 32302442 Check |pmid= value (help).
  30. ↑ Tang N, Bai H, Chen X, Gong J, Li D, Sun Z (2020). "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy". J Thromb Haemost. 18 (5): 1094–1099. doi:10.1111/jth.14817. PMID 32220112 Check |pmid= value (help).
  31. ↑ Akima S, McLintock C, Hunt BJ (2020). "RE: ISTH interim guidance to recognition and management of coagulopathy in COVID-19". J Thromb Haemost. doi:10.1111/jth.14853. PMID 32302442 Check |pmid= value (help).
  32. ↑ Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A; et al. (2016). "Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients". N Engl J Med. 375 (6): 534–44. doi:10.1056/NEJMoa1601747. PMID 27232649.
  33. ↑ Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E; et al. (2020). "COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review". J Am Coll Cardiol. 75 (23): 2950–2973. doi:10.1016/j.jacc.2020.04.031. PMC 7164881 Check |pmc= value (help). PMID 32311448 Check |pmid= value (help).
  34. ↑ https://www.cdc.gov/coronavirus/2019-ncov/index.html. Missing or empty |title= (help)
  35. ↑ "Home care for patients with COVID-19 presenting with mild symptoms and management of their contacts".

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