Heparin-induced thrombocytopenia natural history, complications and prognosis
|
Heparin-induced thrombocytopenia |
|
Differentiating Heparin-induced thrombocytopenia from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Heparin-induced thrombocytopenia natural history, complications and prognosis On the Web |
|
American Roentgen Ray Society Images of Heparin-induced thrombocytopenia natural history, complications and prognosis |
|
FDA on Heparin-induced thrombocytopenia natural history, complications and prognosis |
|
CDC on Heparin-induced thrombocytopenia natural history, complications and prognosis |
|
Heparin-induced thrombocytopenia natural history, complications and prognosis in the news |
|
Blogs on Heparin-induced thrombocytopenia natural history, complications and prognosis |
|
Directions to Hospitals Treating Heparin-induced thrombocytopenia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Shyam Patel [2]
Overview
The natural history of HIT evolves over a period of a few weeks and terminates within 1 year. The development of antibodies to heparin-PF4 is the initial event, the disappearance of these antibodies is the final event. The complications of HIT include thrombotic events and hemorrhagic events. Thrombotic events are more common. The most severe complication of HIT is disseminated intravascular coagulation The prognosis of HIT depends on the presence and severity of thrombosis. If a patient experiences a high degree of thrombotic manifestations, the mortality can be quite high.
Natural History
The natural history of HIT is best defined by specific time points during which key aspects of the disease develop or diminish.
- On day 1 (day of heparin exposure), the process of immune complex formation and antibody formation begins.
- On days 5-14, thrombocytopenia and/or thrombosis can be observed, as this is the time frame during which IgG antibodies recognize the multimolecular complexes and dock onto receptors on platelets, resulting in platelet microgranule release and clot formation.[1]
- Within 1 week of heparin discontinuation, platelet recovery can be seen.[1]
- On weeks 4-6, thrombotic risk continues despite recovery of platelet count, since IgG antibodies to heparin-PF4 are still circulating and still resulting in platelet degranulation.
- On days 85-90, antibody clearance typically occurs, and the risk of thrombosis begins to decrease.
- On day 365, most patients have no remaining HIT antibodies in circulation. However, up to 35% of people can remain seropositive. The natural history of the disease is self-limited. If a patient has recovery of platelet count and no thrombotic events, there are no long-term sequelae of HIT. The risk of HIT with heparin re-exposure in a patient who is seronegative is low. Thus the natural history of the disease does not lead to long-term adverse outcomes.[1]
Complications
Complications of HIT are most thrombotic in nature. These can be quite devastating, which high morbidity and mortality. Venous thrombosis includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Arterial thrombosis includes stroke and acute limb ischemia.
Venous Thrombosis
- Deep vein thrombosis: This is one of the most common manifestations of HIT. It is characterized by acute occlusion of the deep venous system (such as the popliteal vein) by a blood clot. Diagnosis is made via ultrasound of the affected extremity (usually the legs). Treatment involves anticoagulation for at least 3 months. Treatment with anticoagulation helps to prevent ongoing thrombosis formation while the clot naturally dissolves.
- Pulmonary embolism (PE):[2] This is a potentially fatal complication that involves a venous clot that travels to the pulmonary circulation. Though a pulmonary embolism involves a clot in the pulmonary artery, the clot actually origins pathophysiologically from the venous circulation, such as a deep vein of the leg. Diagnosis is made by computed tomography (CT) scan of the chest with intravenous (IV) contrast, which can show hyperdensity in the pulmonary arterial circulation. Treatment involves anticoagulation for at least 3 months. Treatment with anticoagulation helps to prevent ongoing thrombosis formation while the clot naturally dissolves. In the case of hemodynamic compromise (massive PE), thrombolysis can be done (i.e. administration of tissue plasminogen activator (tPA)), which serves to dissolve the clot promptly.
- Post-phlebitis syndrome: This can occur after DVT and results in inflammation of the leg and its veins due to chronic occlusion.
- Cerebral venous sinus thrombosis: This is characterized by clot formation in the veins that encompass the brain, such as the dural venous sinuses. Thrombosis in these veins is otherwise rare but can occur in the setting of a hypercoagulable state such as HIT.
Arterial Thrombosis
- Acute limb ischemia:[2] This can sometimes require limb amputation to prevent further tissue damage and sepsis from the thrombotic arm or leg.
- Stroke:[2] This is due to acute occlusion of vessel in the cerebral arterial system. It can result in permanent neurologic deficits if not treated promptly.
- Myocardial infarction: This is characterized by myocyte death due to ischemic injury from coronary artery occlusion. It is also known more commonly as a heart attack.
- Skin necrosis:[2] This can occur after warfarin is given to a patient with HIT. Warfarin-induced skin necrosis appears to be more common in the context of HIT treatment compared to use of warfarin in the absence of associated HIT.[3] Tissue necrosis an predispose a patient to sepsis and can require amputation or surgical debridement of the affected body part.
Hemorrhagic Complications
- Adrenal hemorrhage[4]: This is a rare but potentially fatal complication of HIT. Hemorrhage occurs due to a combination of initial adrenal venous thrombosis (leading to obstruction of outflow), thrombocytopenia, and impaired normal coagulation. The risk is approximately 1.6% in persons with HIT. It is most commonly associated with a post-operative state (i.e. after an orthopedic surgery) and usually occurs bilaterally (90% of cases).[4] This complication can result in Waterhouse-Friderichsen syndrome, which is characterized by cardiovascular dysfunction resulting in a sepsis-like state.[4] Disseminated intravascular coagulation (DIC) can result if the pathophysiological state continues. Treatment can be challenging since anticoagulation is contraindication in hemorrhage, but ongoing thrombosis can occur if HIT is not treated. The decision about initiating anticoagulation must weight the risks and benefits.
Disseminated Intravascular Coagulation (DIC)
Disseminated intravascular coagulation is a pathologic condition causes by widespread activation of the coagulation cascade with simultaneous consumption of clotting factors. It is characterized by hypercoagulation and hyperfibrinolysis.[4] It can manifest clinically as bleeding, thrombosis, or both. Laboratory findings in DIC include elevation of the partial thromboplastin time (PTT), prothrombin time (PT), and bleeding time, as well as thrombocytopenia.[4] Treatment aims at addressing the underlying hemostatic or coagulopathic state: if a patient is bleeding, blood products should be administered. If a person has ongoing clotting, anticoagulation should be administered.
Prognosis
The prognosis is HIT depends on the degree of thrombocytopenia and thrombotic complications.
- For patients with severe thrombosis, the morbidity and mortality can be high. Prognosis is poor for patients who have hemodynamically significant clot burden, such as massive pulmonary embolism (PE) or acute vascular occlusion involves the brain.
- For patients with no thrombosis, if HIT resolves without thrombotic complications and with recovery of platelet count, the prognosis is excellent. Patients can survive long-term after HIT resolves with no functional limitations.
Reference
- ↑ 1.0 1.1 1.2 Arepally GM, Ortel TL (2010). "Heparin-induced thrombocytopenia". Annu Rev Med. 61: 77–90. doi:10.1146/annurev.med.042808.171814. PMC 4153429. PMID 20059332.
- ↑ 2.0 2.1 2.2 2.3 Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S; et al. (2012). "Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e495S–e530S. doi:10.1378/chest.11-2303. PMC 3278058. PMID 22315270.
- ↑ Fawaz B, Candelario NM, Rochet N, Tran C, Brau C (2016). "Warfarin-induced skin necrosis following heparin-induced thrombocytopenia". Proc (Bayl Univ Med Cent). 29 (1): 60–1. PMC 4677858. PMID 26722173.
- ↑ 4.0 4.1 4.2 4.3 4.4 Tattersall TL, Thangasamy IA, Reynolds J (2014). "Bilateral adrenal haemorrhage associated with heparin-induced thrombocytopaenia during treatment of Fournier gangrene". BMJ Case Rep. 2014. doi:10.1136/bcr-2014-206070. PMC 4202074. PMID 25315802.