Thrombophilia classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Asiri Ediriwickrema, M.D., M.H.S. [2]

Overview

Thrombophilias are classified as either inherited or a primary hypercoagulable state, acquired or a secondary hypercoagulable state, or mixed/unknown. Certain conditions are associated with greater thrombotic risks and both venous and arterial clots.

Classification

• Thrombophilia can be classified in various forms.

• Inherited thrombophilia or primary hypercoagulable state
• Acquired thrombophilia or secondary hypercoagulable state
• Mixed/Unknown
• Venous verse arterial clots

Thrombophilia Classification
Inherited (Primary)	Acquired (Secondary)	Mixed/Unknown
Activated protein C (APC) resistance (Factor V Leiden)	Age	Hyperhomocysteinemia
Prothrombin gene mutation (Prothrombin G20210A)	Immobilization	APC resistance unrelated to Factor V Leiden.
Antithrombin deficiency	Trauma/major surgery	Increased factor VIII level
Protein C and protein S deficiency	Orthopedic surgery	Increased factor XI level
Dysfibrinogenemia	Malignancy	Increased factor IX level
	Myeloproliferative disorders (polycythemia vera, essential thrombocythemia, hyperviscosity)	Increased levels of thrombin-activatable fibrinolysis inhibitor (TAFI)
	Pregnancy	Decreased levels of free tissue factor pathway inhibitor (TFPI)
	Estrogen and testosterone (oral contraceptives and hormone replacement therapy)
	Obesity
	Heart Failure
	Cirrhosis
	Chronic renal disease (nephrotic syndrome)
	Antiphospholipid syndrome (APLS) or lupus anticoagulant
	Heparin induced thrombocytopenia (HIT)
	Disseminated intravascular coagulopathy (DIC)
	Paroxysmal nocturnal hemoglobinuria (PNH)
	Vasculitis
	Thrombotic microangiopathy
	Drug related (chemotherapies including L-aspariginase, mitomycin, infusion of clotting factors including prothrombin complex concentrates, cryoprecipitate)

Thrombophilic states associated with arterial clots
APLS and lupus anticoagulant
HIT
DIC
PNH
Cold agglutinins (associated with mycoplasma infections)
Vasculitis
Hyperhomocysteinemia

Thrombophilic state	Thrombotic risk
Trauma/General surgery	Modest
Age > 60	Modest
Immobilization	Modest
Pregnancy	Modest
Hormone therapies	Modest
Factor V Leiden	Modest
Prothrombin mutation	Modest
Homocysteinemia	Modest
Protein C and S deficiency	Intermediate
Malignancy	High
APLS/Lupus anticoagulant	High
Myeloproliferative disorders/hyperviscosity	High
PNH	High
Orthopedic surgery	High
Antithrombin deficiency	High

• Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

• The most common classification is by the nature of the thrombosis: arterial, venous or combined.