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Thrombosis, Thrombophilia, and Thromboembolism

  • Clinical Updates in Women's Health Care CU
  • May 2016

ABSTRACT: Obstetrician–gynecologists are uniquely positioned to identify patients at risk of venous thromboembolism, a leading cause of morbidity and mortality in women. Pregnancy, use of exogenous estrogen, and gynecologic surgery represent three of the most provocative stimuli for venous thromboembolism; therefore, obstetrician–gynecologists should be aware of these and other risk factors, so that preventive measures can be implemented. Furthermore, because venous thromboembolism is increasingly common in these three clinical settings, it is important that obstetrician–gynecologists be fully versed in the diagnosis and treatment of venous thromboembolism.

This monograph describes the basic elements of the coagulation system, risk factors, and diagnostic algorithms for venous thromboembolism as well as various therapeutic agents available to treat venous thromboembolism. Strategies for screening patients who require gynecologic surgery, are planning pregnancy, are currently pregnant, or are using estrogen-containing hormone therapy (HT) also are described.

Venous thromboembolism is a leading cause of death in women 1. Its two principal presentations are 1) deep vein thrombosis (DVT), usually in leg veins, and 2) acute pulmonary embolism (PE). Approximately 90% of cases of the acute PE arise from DVT, particularly when proximal leg veins are the sites of the initial thrombus. The overall annual incidence of venous thromboembolism in the United States has been estimated to be 1.45 per 1,000 individuals, with DVT occurring in 4.8 per 10,000 individuals and acute PE in 2.3 per 10,000 individuals 1. The prevalence of both conditions increases markedly with increasing age. Patients with DVT also are at risk of chronic postphlebitic syndrome, characterized by venous ulceration, pain, and edema. Furthermore, based on claims data, the prevalence of venous thromboembolism is estimated to increase from 0.95 million in 2006 to 1.82 million in 2050 in the United States 2. This increase primarily reflects the aging of the population. Given the substantial mortality and morbidity associated with venous thromboembolism in women and the pathologic contributions of pregnancy, use of exogenous estrogen, and gynecologic surgery, it is important that obstetrician–gynecologists take the lead in identifying patients at risk, implementing preventive measures, promptly diagnosing thrombotic events, and ensuring that therapy is expeditiously initiated.

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Figures & Tables

Fig. 1. Platelet plug formation after vascular injury. Abbreviations: ADP indicates adenosine diphosphate; PAF, platelet activating factor; TF, tissue factor; TXA 2 , thromboxane.

Fig. 1. Platelet plug formation after vascular injury. Abbreviations: ADP indicates adenosine diphosphate; PAF, platelet activating factor; TF, tissue factor; TXA 2 , thromboxane.

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Fig. 2. Anticoagulant system. Abbreviations: aPC indicates activated protein C; EPCR, endothelial protein C receptor; FDP, fibrin degradation product; PAI, plasminogen activator inhibitor; PC, protein C; PS, protein S; PZ, protein Z; TAFI, thrombin-activatable fibrinolysis inhibitor; TF, tissue factor; TFPI, tissue factor pathway inhibitor; tPA, tissuetype plasminogen activator; uPA, urokinase-type plasminogen activator; ZPI, Z-dependent protease inhibitor.

Fig. 2. Anticoagulant system. Abbreviations: aPC indicates activated protein C; EPCR, endothelial protein C receptor; FDP, fibrin degradation product; PAI, plasminogen activator inhibitor; PC, protein C; PS, protein S; PZ, protein Z; TAFI, thrombin-activatable fibrinolysis inhibitor; TF, tissue factor; TFPI, tissue factor pathway inhibitor; tPA, tissuetype plasminogen activator; uPA, urokinase-type plasminogen activator; ZPI, Z-dependent protease inhibitor.

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Fig. 3. Workup of suspected deep vein thrombosis (assumes availability of a sensitive test for D-dimers).

Fig. 3. Workup of suspected deep vein thrombosis (assumes availability of a sensitive test for D-dimers).

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Fig. 4. Alternative diagnostic paradigm for the diagnosis of deep vein thrombosis when D-dimer test is unavailable or inappropriate.

Fig. 4. Alternative diagnostic paradigm for the diagnosis of deep vein thrombosis when D-dimer test is unavailable or inappropriate.

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Fig. 5. Diagnostic algorithm to rule out acute pulmonary embolism in a high-risk nonpregnant patient. Abbreviations: CT indicates computed tomography; V ̇ / Q ̇ , ventilation–perfusion.

Fig. 5. Diagnostic algorithm to rule out acute pulmonary embolism in a high-risk nonpregnant patient. Abbreviations: CT indicates computed tomography; V ̇ / Q ̇ , ventilation–perfusion.

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Fig. 6. Testing paradigm for the 25–65% of patients with suspected acute pulmonary embolism who are assigned into the low (5–10%) clinical probability group when D-dimer testing is available and appropriate.

Fig. 6. Testing paradigm for the 25–65% of patients with suspected acute pulmonary embolism who are assigned into the low (5–10%) clinical probability group when D-dimer testing is available and appropriate.

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Fig. 7. Testing paradigm for the 25–65% of patients with suspected acute pulmonary embolism who are assigned into the low (5–10%) clinical probability group when D-dimer testing is un available or not appropriate or when test results are positive. Abbreviation: CT indicates computed tomography; V ̇ / Q ̇ , ventilation–perfusion.

Fig. 7. Testing paradigm for the 25–65% of patients with suspected acute pulmonary embolism who are assigned into the low (5–10%) clinical probability group when D-dimer testing is un available or not appropriate or when test results are positive. Abbreviation: CT indicates computed tomography; V ̇ / Q ̇ , ventilation–perfusion.

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Fig. 8. Workup of the 25–65% of patients with suspected acute pulmonary embolism who are assigned into the intermediate (25–45%) clinical risk category. Abbreviation: V ̇ / Q ̇ indicates ventilation–perfusion.

Fig. 8. Workup of the 25–65% of patients with suspected acute pulmonary embolism who are assigned into the intermediate (25–45%) clinical risk category. Abbreviation: V ̇ / Q ̇ indicates ventilation–perfusion.

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Fig. 9. Diagnostic workup of a pregnant patient with suspected acute pulmonary embolism.

Fig. 9. Diagnostic workup of a pregnant patient with suspected acute pulmonary embolism.

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Table 1. Inherited Thrombophilias and Their Association With Venous Thromboembolism

Table 1. Inherited Thrombophilias and Their Association With Venous Thromboembolism

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Table 2. Inherited Thrombophilias and Their Association With Venous Thromboembolism in Pregnancy

Table 2. Inherited Thrombophilias and Their Association With Venous Thromboembolism in Pregnancy

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Table 3. Duration of Oral Anticoagulant Therapy by Clinical Setting

Table 3. Duration of Oral Anticoagulant Therapy by Clinical Setting

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Table 4. Risk Classification for Venous Thromboembolism in Patients Who Undergo Surgery Without Prophylaxis

Table 4. Risk Classification for Venous Thromboembolism in Patients Who Undergo Surgery Without Prophylaxis

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Table 5. Deep Vein Thrombosis Clinical Characteristic Score

Table 5. Deep Vein Thrombosis Clinical Characteristic Score

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Table 6. Acute Pulmonary Embolism Clinical Characteristic Risk Score

Table 6. Acute Pulmonary Embolism Clinical Characteristic Risk Score

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Table 7. Likelihood of Acute Pulmonary Embolism According to Ventilation–Perfusion Scan Results and Patient Clinical Risk Category

Table 7. Likelihood of Acute Pulmonary Embolism According to Ventilation–Perfusion Scan Results and Patient Clinical Risk Category

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Table 8. Weight-Based Nomogram for Intravenous Unfractionated Heparin Administration

Table 8. Weight-Based Nomogram for Intravenous Unfractionated Heparin Administration

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Table 9. Dosage-Based Protocol for Intravenous Unfractionated Heparin Administration

Table 9. Dosage-Based Protocol for Intravenous Unfractionated Heparin Administration

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