Bleeding diathesis

Bleeding diathesis main page
Overview
Classification
Differential Diagnosis Platelet disorders Immune Thrombocytopenic Purpura Thrombotic Thrombocytopenic Purpura Hemolytic Uremic Syndrome Thrombocytosis Von Willebrand Disease
Coagulation disorders Fibrinogen deficiency Prothrombin deficiency Factor V deficiency Factor VII deficiency Factor VIII deficiency Factor IX deficiency Factor X deficiency Factor XI deficiency Factor XII deficiency High-molecular-weight kininogen deficiency Prekallikrein deficiency Factor XIII deficiency Hemophilia
Rare diseases Disseminated Intravascular Coagulation Vitamin K Deficiency
Different types of Von-Willebrand diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Mehrian Jafarizade, M.D [2], Nazia Fuad M.D.

Overview

Bleeding diathesis is unusual susceptibility to bleed due to hypo-coagulopathies. These diseases can occur due to a disorder of homeostasis, localized process (tissue injury), or medications. Bleeding diathesis can be resulted from vessel wall injury, platelet disorders, and coagulation factor disorders. Clinical manifestation of bleeding disorders can have a wide range of symptoms from asymptomatic to symptomatic massive and life threatening bleeding. Platelet disorders mostly have skin manifestations such as petechiae, and ecchymoses. In order to find the cause of hypo-coagulopathy, there are established laboratory tests that might be used. These laboratory tests such as peripheral blood smear, platelet count and platelet function analysis, coagulation factor deficiencies and inhibitors, fibrinolysis tests (eg. D-dimer level), bleeding time, prothrombin time, activated partial thromboplastin time, thrombin time and reptilase time.

Classification

Different categories of diseases can cause bleeding disorders. These categories can be classified as below:

1. Platelet disorders:
   • Thrombocytopenia: platelet count less than 150,000 per mm³
   • Thromobcytosis: platelet countcmore than 450,000 per mm³
   • Qualitative Disorders of Platelet function such as Von Willebrand Disease, inherited or acquired functional disorders.
2. Vessel wall disorders: Endothelial cells are lining entire vessel walls all over the body. Endothelium is an active layer responsible for inflammatory responses, angiogenesis and blood cell interactions. Endothelial cells have a very important role in hemostasis and they are regulating blood fluidity by the balance of antithrombotic/prothrombotic and vasodilatory/vasoconstrictor effects.
   • Metabolic and Inflammatory Disorders
   • Inherited Disorders of the Vessel Wall
3. Coagulation factor disorders:
   • Fibrinogen deficiency
   • Prothrombin deficiency
   • Factor V deficiency
   • Factor VII deficiency
   • Factor X deficiency
   • Factor XII deficiency
   • HK deficiency
   • Prekallikrein deficiency
   • Factor XIII deficiency
   • Hemophilia
4. Disseminated Intravascular Coagulation
5. Vitamin K Deficiency
6. Coagulation Disorders Associated with Liver Failure
7. Acquired Inhibitors of Coagulation Factors

Differential Diagnosis

Category	Sub-category	Diseases	History	Clinical manifestation					Laboratory testing					Comments
				Petechiae	Ecchymoses	Menorrhagia	Hematomas	Hemarthrosis	platelet count	Bleeding time (BT)	Prothrombin time (PT)	Platelet count activated partial thromboplastin time (aPTT)	Thrombin time (TT)
Platelet disorders	Thrombocytopenia	Infection-Induced Thrombocytopenia	History of prior infection	+	+				↓		N	N
		Medications-Induced Thrombocytopenia	History of medications	+	+				↓		N	N
		Heparin-Induced Thrombocytopenia	Thrombosis Unexplained thrombocytopenia up to 3 weeks after the end of heparin therapy	+	+				↓
		Immune Thrombocytopenic Purpura (ITP)		+	+				↓	↑	N	N
		Inherited Thrombocytopenia							↓	↑	N	N
		Thrombotic Thrombocytopenic Purpura (TTP)								↑
		Hemolytic Uremic Syndrome									N	N
	Thromobcytosis		Digital pain Gangrene Erythromelalgia Headache Paresthesias Transient ischemic attacks	−	−	−	+	+	↑	ɴormal or slightly prolonged	ɴ	ɴ
	Qualitative Disorders of Platelet Function	Inherited Disorders of Platelet Function
		Acquired Disorders of Platelet Function
		Von Willebrand Disease	Easy bruising Epistaxis Oral cavity bleeding Bleeding after dental extraction/surgery Menorrhagia Postpartum hemorrhage	+	+	+	+	+	↑	Ν	↑	↑
Vessel wall disorders	Metabolic and Inflammatory Disorders
	Inherited Disorders of the Vessel Wall
Coagulation factor disorders	Fibrinogen deficiency		Epistaxis Easy bruising Menorrhagia Muscle bleeds Hemarthrosis Bleeding from the umbilical cord stump after birth Bleeding after dental surgery or tooth extraction Abnormal bleeding during or after injury, surgery, or childbirth Gastrointestinal hemorrhage Cerebral hemorrhage Thrombosis	_	+	+		+	N	↑	↑	↑	↑	The severity of bleeding in patients with fibrinogen disorders can be mild or severe, with higher bleeding risk in those with afibrinogenemia or lower levels of functional fibrinogen. The age of onset is also variable, with earlier onset in those with more severe deficiency.
	Prothrombin deficiency		Easy bruising Epistaxis Soft-tissue hemorrhage Excessive postoperative bleeding Menorrhagia Muscle hematomas Hemarthrosis Intracranial bleeding	+	+	+	+	+	N	N	↑	↑	↑
	Factor V deficiency
	Factor VII deficiency
	Factor X deficiency
	Factor XII deficiency
	HK deficiency
	Prekallikrein deficiency
	Factor XIII deficiency
	Hemophilia	Type A deficiency	Eeasy bruising Inadequate clotting in trauma or mild injury Spontaneous hemorrhage. Hemarthrosis Epistaxis Gingival bleeding	_	_	+	+	+	Unaffected	Unaffected	Unaffected	Prolonged	N
		Type B deficiency	Neonatal bleeding Trauma-related soft-tissue hemorrhage Hemarthrosis Hematomas	_	_	+	+	+	Unaffected	N	N	↑	N
		Type C deficiency	Family history of bleeding disorder, Bleeding after surgry or injury	_	_	+	Rare	Rare	N	N	N	↑	N
Rare diseases	Disseminated Intravascular Coagulation		Trauma Burn Crush injury Sepsis Malignancy Obstetric complication: abruption, amniotic fluid embolism Hemolytic anemia	+	+	_	+	+	↓	↑	↑	↑
	Vitamin K Deficiency		Bleeding after trauma Epistaxis Hematoma Gastrointestinal bleeding, Menorrhagia Hematuria Gum bleeding Oozing from venipuncture sites Easy bruisability	+	+	+	+	+	N	↑	↑	Normal or mildly prolonged
	Coagulation Disorders Associated with Liver Failure
	Acquired Inhibitors of Coagulation Factors

Different types of Von willebrand diseases can be differentiate from each other based on below table:

Type of VWD		Type of factor deficiency	Prevalence	Inheritance pattern	Clinical manifestations	VWF activity	RIPA	Factor VIII	Plt levels
Type 1		Quantitative/ partial
Type 2	2A
	2B
	2M
	2N
Type 3