Hypercoagulable States

Published on 04/03/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

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Chapter 63 Hypercoagulable States

Julia A. Anderson, Jeffrey I. Weitz

Table 63-1 Classification of Hypercoagulable States

Table 63-2 Types of Inherited Antithrombin Deficiency

Table 63-3 Causes of Acquired Antithrombin Deficiency

Decreased Synthesis	Increased Consumption	Enhanced Clearance
Hepatic cirrhosis	Major surgery	Heparin
Severe liver disease	Acute thrombosis	Nephrotic syndrome
l-asparaginase	Disseminated intravascular coagulation
	Severe sepsis
	Multiple trauma
	Malignancy
	Prolonged extracorporeal circulation

Figure 63-1 THROMBOSIS THRESHOLD.

Genetic and acquired risk factors continue to determine an intrinsic risk for thrombosis for each individual. This risk is increased by extrinsic or environmental factors and decreased by thromboprophylaxis. If the intrinsic and extrinsic forces exceed a critical threshold at which thrombin generation overwhelms the protective mechanisms, thrombosis will result.

(From Anderson JA, Weitz JI: Hypercoagulability and uncommon vascular diseases. In Jaff MR, White CJ, editors: Vascular disease: Diagnostic and therapeutic approaches, Minneapolis, Minn, 2011, Cardiotext Publishing.)

Figure 63-2 PROTEIN C PATHWAY.

Activation of coagulation triggers thrombin (IIa) generation. Excess thrombin binds to thrombomodulin (TM) on the endothelial cell surface. Once bound, the substrate specificity of thrombin is altered so that it no longer acts as a procoagulant but becomes a potent activator of protein C (PC). Endothelial protein C receptor (EPCR) binds protein C and presents it to thrombomodulin-bound thrombin, where it is activated. Activated protein C (APC), together with its cofactor, protein S (PS), binds to the activated platelet-surface and proteolytically degrades factor Va (Va) into inactive fragments (Vi). Because factor Va is a critical component of the prothrombinase complex, factor Va inactivation by activated protein C attenuates thrombin generation. Because factor Va_Leiden (FVa_L) is resistant to inactivation by activated protein C, patients with the factor V_Leiden mutation have reduced capacity to regulate thrombin generation.

Table 63-4 Types of Inherited Protein C Deficiency

Type	Antigen	Activity
I	Low	Low
II	Normal	Low

Table 63-5 Types of Inherited Protein S Deficiency

Table 63-6 Features of Heparin-Induced Thrombocytopenia

Feature	Details
Thrombocytopenia	Platelet count of 100,000/µl or less or a decrease in platelet count of 50% or more
Timing	Platelet count falls 5 to 10 days after starting heparin
Type of heparin	More common with unfractionated heparin than LMWH
Type of patient	More common in surgical patients than medical patients; more common in women than in men
Thrombosis	Venous thrombosis more common than arterial thrombosis

Routine Investigations to Evaluate a Patient With (Venous) Thrombosis

Test	Abnormality	Diagnostic Information
Complete blood count	Elevated hematocrit Increased white count Increased platelet count Leukopenia Thrombocytopenia	Myeloproliferative disorder (e.g., essential thrombocythemia, polycythemia vera); may be found in paroxysmal nocturnal hemoglobinuria; if associated with heparin administration, consider heparin-induced thrombocytopenia
Blood film	Leukoerythroblastic film	Underlying neoplasm invading bone marrow
Liver function tests	Abnormal tests	May point to malignancy
Renal function	Impaired renal function	Assess prior to anticoagulation with heparin or LMWH
Urinalysis	Proteinuria	Nephrotic syndrome; may be associated with venous thromboembolism or renal vein thrombosis
PT and aPTT	Prolonged PT and aPTT	To enable safe anticoagulation to proceed if required Need to exclude lupus anticoagulant