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]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2], Nazia Fuad M.D., Sogand Goudarzi, MD [3]

Synonyms and keywords: Hypocoagulopathy; blood coagulation disorders; hemorrhagic diathesis; hemostasis abnormality; bleeding tendency

Overview

Bleeding diathesis is susceptibility to bleed due to coagulopathy disorders or platelets disorders. 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, such as peripheral blood smear, platelet count and platelet function analysis, coagulation factor deficiencies and inhibitors, fibrinolysis tests (eg. D-dimer level), bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and reptilase time. In the case of any abnormal bleeding, first line of screening tests are CBC, PT, PTT, BT, and TT.

Classification

Disorders of hemostasis can be classified into two main categories: platelet disorders, and disorders of coagulation. Each category can be further classified as bellow:

Abnormal hemostasis

• Patient history-sign & symptom: deep soft tissue & mucocutaneus bleeding • Screen test CBC-Plt-PT&PTT-BT-TT

Hx of deep soft tissue bleeding

Hx of mucocotaneus bleeding

Coagulopathy

Plt disorder

Family history

Normal plt count

Low plt count

(+) • Inherited coagulpathy

(-) • Acquired coagulopathy

Functional Plt disorder

↑Plt • Hemophillia • VWD • Factor VIII or IX deficiency

↑PT • Factor VII deficiency

↑PT&↑PTT • Fibrinogen deficiency • Factor II deficiency • Factor V deficiency • Factor X deficiency

↑PTT • Factor inhibitor • Anti phospholipid Ab syndrome

↑PT • Factor inhibitor • Vit K deficiency • Liver disease

↑PT&↑PTT • Factor inhibit • DIC • Liver failure • Late stage of Vit K deficiency

↑ Afibrinogenemia • Heparin inhibitor • Direct thrombin inhibitor

Abnormal solobity • Factor XIII deficiency • Cross-linkin inhibitor

Not corrected with mixing with NL plasma

HX(+)

HX(-)

• Factor inhibitors • Lupus anti coagulant • DIC • Heparin or direct thrombin inhibitors

Congenital

Acquired

Differentiating Bleeding Disorders from Other Diseases

Different causes of bleeding disorders can be differentiated based on their clinical manifestation and laboratory findings.

These features have discussed in the below table:

Category	Subcategory	Disease		History	Clinical manifestation						Laboratory testing					Comments
					Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT
Platelet disorders	Thrombocytopenia	Infection-Induced thrombocytopenia		History of prior infection	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Medication-Induced Thrombocytopenia		History of medications such as: Furosemide Nonsteroidal anti-inflammatory drugs (NSAIDs) Penicillin Quinidine Quinine Ranitidine Sulfonamides Linezolid	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	Most important part of treatment is discontinuing of the medication.
		Heparin-Induced thrombocytopenia		Thrombosis Unexplained thrombocytopenia up to 3 weeks after the end of heparin therapy	+	+	+	+	+	+	↓	↑	Nl	Nl	↑	For more information click here: Heparin-induced thrombocytopenia.
		Immune Thrombocytopenic Purpura		History of prior infection or no history	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Inherited Thrombocytopenia		Positive family history	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Thrombotic Thrombocytopenic Purpura		History of: Cancer Bone marrow transplantation Pregnancy Medication Platelet aggregation inhibitors (ticlopidine and clopidogrel) Immunosuppressants (cyclosporine, mitomycin, tacrolimus/FK506, interferon-α) HIV-1 infection	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Hemolytic Uremic Syndrome		History of: Infections Malignancy, chemotherapy, and ionizing radiation Calcineurin inhibitors and transplantation Pregnancy, HELLP syndrome, and oral contraceptive pill Systemic lupus erythematosis Antiphospholipid antibody syndrome Glomerulopathy	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
	Thromobcytosis	Iron deficiency anemia Inflammatory diseases Splenectomy Essential thrombocytosis		Digital pain Gangrene Erythromelalgia Headache Paresthesias Transient ischemic attacks	−	−	−	−	±	±	↑	Nl or ↑	Nl	Nl	Nl	−
	Qualitative Disorders of Platelet Function	Inherited Disorders of Platelet Function	Glanzmann’s thrombasthenia	Positive family history	+	+	+	+	−	Rare	Nl or ↓	↑	Nl	Nl	Nl	AR inheritance Absence of the platelet Gp IIb/IIIa receptor Diminished for GP 2B-3A on flow cytometry
			Bernard-Soulier syndrome	Positive family history	+	+	+	+	−	−	Nl or ↓	↑	Nl	Nl	Nl	AR inheritance Absence of the platelet Gp Ib-IX-V receptor On PBS: giant platelets Ristocetin - no aggregation
			Wiskott-Aldrich syndrome	Positive family history	+	+	+	+	−	−	Nl or ↓	↑	Nl	Nl	Nl	Anti-WASP antibody can be used to detect presence or absence of WAS protein In Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.
			Platelet storage pool disorder: Hermansky-Pudlak syndrome Chediak-Higashi syndrome Gray platelet syndrome	Positive family history Hairy cell leukemia Cardiovascular bypass	+	+	+	+	−	−	Nl or ↓	↑	Nl	Nl	Nl	AD inheritance Abnormlities of platelet granule formation
		Acquired Disorders of Platelet Function		Uremia Cardiopulmonary bypass Hematologic disorders such as: myeloproliferative and myelodysplastic syndromes	+	+	+	+	±	±	Nl or ↓	↑	Nl	Nl	Nl	−
		Von Willebrand Disease		Easy bruising Epistaxis Oral cavity bleeding Bleeding after dental extraction/surgery Menorrhagia Postpartum hemorrhage	+	+	+	+	±	±	↑	Nl	↑	↑	Nl	See the table below for the details about different types.
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
Vessel wall disorders	Metabolic and Inflammatory Disorders	Acute febrile illnesses Mixed cryoglobulinemia Monoclonal gammopathies Rocky Mountain spotted fever Vitamin C deficiency Cushing’s syndrome Chronic glucocorticoid therapy Vasculitis such as Henoch-Schönlein Purpura		History of the underlying disease	−	+	+	±	−	−	Nl	Nl or ↑	Nl	Nl	Nl	−
	Inherited Disorders of the Vessel Wall	Marfan’s syndrome Ehlers-Danlos syndrome Pseudoxanthoma elasticum Hereditary hemorrhagic telangiectasia (HHT, or Osler-Weber-Rendu disease)		Positive family history	−	+	+	±	−	−	Nl	Nl or ↑	Nl	Nl	Nl	−
Coagulation factor disorders	Fibrinogen deficiency	Different types of the fibrinogen disorders: Congenital afibrinogenemia Congenital hypofibrinogenemia Fibrinogen storage disease Congenital dysfibrinogenemia Hereditary fibrinogen Aα-Chain amyloidosis Acquired dysfibrinogenemia		Epistaxis Easy bruising Menorrhagia Muscle bleeds Hemarthrosis Bleeding from the umbilical cord stump after birth Bleeding after dental surgery or tooth extraction AbNl bleeding during or after injury, surgery, or childbirth Gastrointestinal hemorrhage Cerebral hemorrhage Thrombosis	−	−	+	+	±	+	Nl	↑	↑	↑	↑	Impaired fibrin cross-linking or clot dissolution Mild or severe bleeding depend on levels of functional fibrinogen Variable age of onset
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
	Prothrombin deficiency			Epistaxis Soft-tissue hemorrhage Excessive postoperative bleeding Menorrhagia Muscle hematomas Hemarthrosis Intracranial bleeding	−	+	+	+	+	+	Nl	Nl	↑	↑	↑	−
	Factor V deficiency			Excessive bruising with minor injuries Epistaxis Hemarthrosis Menorrhagia Intracerebral hemorrhages Pulmonary hemorrhage	−	−	+	+	+	+	Nl	↑	↑	↑	Nl	The severity of bleeding related to the degree of factor V deficiency
	Factor VII deficiency			Easy bruising Mucosal bleeding Postoperative bleeding Menorrhagia Soft tissue hematomas Thrombosis				+	+	+	Nl		↑	Nl	Nl	Thrombosis in inherited factor VII deficiency Treatment with the administration of factor VII replacement therapy
	Factor X deficiency			Prolonged bleeding following circumcision Easy bruising Hematuria Menorrhagia Abortion Postpartum hemorrhage Epistaxis Pseudotumors Intracranial bleeding Hemarthroses		+	+	+	+	+	Nl	Nl	↑	↑	Nl	−
	Factor XII deficiency			Asymptomatic Recurrent miscarriages Painful leg ulcers		−	−	−	−	−	Nl	Nl	Nl	↑	Nl
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
	High molecular weight kininogen (HMWK) deficiency			Positive family history of bleeding		−	−	−	−	−	Nl	Nl	Nl	↑	Nl
	Prekallikrein deficiency			Positive family history of bleeding		−	−	−	−	−	Nl	Nl	Nl	↑	Nl
	Factor XIII deficiency	Sub unit A mutation disease (more common) Sub unit B mutation disease		Positive family history of bleeding	±	±	±	±	±	±	Nl	Nl	Nl or ↑	Nl	Nl	Impaired fibrin cross-linking or clot dissolution The severity of factor XIII deficiency bleeds can be different in different patients
	Hemophilia	Type A deficiency		Eeasy bruising Inadequate clotting in trauma or mild injury Spontaneous hemorrhage Hemarthrosis Epistaxis Gingival bleeding	−	−	−	+	+	+	Nl	Nl	Nl	↑	Nl	−
		Type B deficiency		Neonatal bleeding Trauma-related soft tissue hemorrhage Hemarthrosis Hematomas	−	−	−	+	+	+	Nl	Nl	Nl	↑	Nl	−
		Type C deficiency		Positive family history Bleeding after surgery or injury	−	−	−	+	Rare	Rare	Nl	Nl	Nl	↑	Nl	−
	Subcategory	Disease		History	Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Plt	BT	PT	PTT	TT	Comments
Rare diseases	Disseminated Intravascular Coagulation			Trauma Burn Crush injury Sepsis Malignancy Obstetric complication: abruption, amniotic fluid embolism Hemolytic anemia	+	+	+	+	+	+	↓	↑	↑	↑	Nl	−
	Vitamin K Deficiency			Bleeding after trauma Epistaxis Hematoma Gastrointestinal bleeding Menorrhagia Hematuria Gum bleeding Oozing from venipuncture sites Easy bruisability	+	−	+	+	+	+	Nl	↑	↑	Nl or mildly prolonged	Nl	−

Different types of Von-Willebrand diseases

Type of VWD		Type of factor deficiency	Prevalence	Inheritance pattern	Clinical manifestations	VWF activity	RIPA	Factor VIII
Type 1		Quantitative/ partial	60-70%	AD	Bleeding severity mild to severe	↓	↓	↓
Type 2	2A	Qualitative	10%	AD/AR	Moderate to severe bleeding	↓	↓	N or ↓
	2B	Qualitative	5%	AD	Thrombocytopenia Moderate to severe bleeding	↓	↑	N or ↓
	2M	Qualitative	<1%	AD/AR	Moderate to severe bleeding	↓	↓	N or ↓
	2N	Qualitative	<1%	AR	Clinically similar to hemophilia A with joint, soft tissue, urinary bleeding	N	N	↓
Type 3		Complete deficiency	1-2%	AR	Clinically similar to hemophilia A with joint and soft tissue bleeding Severe mucosal bleeding	Absent	↓	Low, 1-10%

For more information on Von Willebrand disease, click here.