Definition
A.Strictly speaking, coagulopathy describes a condition that disturbs the blood’s ability to clot. For purposes of this text, coagulopathy will refer to hypercoagulability. Bleeding disorders are described elsewhere in this chapter.
B.Hypercoagulability, sometimes referred to as thrombophilia, is an enhanced state of hemostasis that increases the risk for thrombosis and blood vessel occlusion.
C.These conditions are typically created in the presence of increased platelet function or increased activity of the coagulation system. Arterial thrombi are most often associated with turbulent blood flow and are composed of platelets.
D.Hypercoagulability disorders have been characterized as primary (hereditary) or secondary (acquired).
Incidence
A.Approximately 30% of those who present with deep vein thrombosis or pulmonary emboli are found to have Factor V Leiden. Factor V Leiden is seen primarily in individuals of European descent and in approximately 5% of whites in the United States.
B.Antiphospholipid antibodies are present in 3% to 5% of the general population and are more prevalent in individuals with systemic lupus erythematosus.
C.Venous thromboembolism (VTE) is not uncommon in the presence of malignancy. Tumor type and stage, location of the tumor, treatment, and comorbid conditions influence risk. It is estimated that as many as 10% of cancer patients develop VTE.
Pathogenesis
A.Most hereditary thrombophilic disorders are associated with mutations in coagulation proteins, fibrinolytic proteins, platelet receptors, and various other factors. Factor V Leiden, a condition in which a Factor V mutation interacts with protein C, leading to increased clot formation, is the most common hereditary condition.
B.Other inherited hypercoagulable states are rarer and include prothrombin gene mutation, hyperhomocysteinemia, antithrombin deficiency, and protein C and protein S deficiency.
C.Antiphospholipid syndrome is the most common acquired hypercoagulable condition. When present, antiphospholipid antibodies are directed against phospholipid–protein complexes causing risk for both arterial and venous thrombus formation.
D.Protein C and protein S deficiency may also become acquired in some disease states.
E.Increased platelet function may manifest as enhanced platelet adhesion, with clot formation and decreased blood flow. Disturbances in blood flow, as with a therosclerotic plaques, cause endothelial tissue damage. Increased sensitivity of platelets to substances that influence platelet aggregation may increase platelet activity.
F.Elevation in platelet counts above 1,000,000/µL, referred to as thrombocytosis, is associated with both thrombosis and bleeding. Primary thrombocytosis is a myeloproliferative disorder associated with a disorder of hematopoietic cells in the bone marrow. Secondary thrombocytosis is often associated with disease states that trigger thrombopoietin production, increasing platelet production. These conditions include surgery, cancer, and chronic inflammatory disorders.
Predisposing Factors
A.Surgery.
B.Cancer.
C.Chronic inflammatory disorders.
D.Atherosclerosis.
E.Diabetes mellitus.
F.Smoking.
G.Pregnancy.
H.Oral contraceptive use.
I.Estrogen replacement therapy.
J.Obesity.
K.Heart failure.
L.Nephrotic syndrome.
M.Polycythemia.
N.Sickle cell disease.
Subjective Data
A.Common complaints/symptoms.
1.Patients with thrombocytosis may experience painful burning and throbbing in digits associated with arteriole occlusion.
2.Painful, swollen extremity (usually unilateral).
B.Common/typical scenario.
1.Other signs and symptoms.
a.Neurological impairment consistent with transient ischemic attack or stroke.
b.Chest pain associated with cardiac ischemia.
c.Dyspnea associated with pulmonary emboli.
d.Visual disturbance with retinal ischemia.
C.Family and social history.
1.History of fetal loss in women with antiphospholipid syndrome.
2.History of unprovoked thrombosis in adults under 45 years of age.
3.Family history of multiple individuals with VTE.
D.Review of systems.
1.Hematologic: Ask about bruising or previous clotting episodes of the arterial or venous system, such as stroke, myocardial infarction, or small vessel thrombosis.
2.Rheumatology: Ask about autoimmune disorders.
3.Obstetrics: Ask about spontaneous abortions.
4.Dermatology: Ask about skin discoloration.
Physical Examination
A.Physical examination may yield nonspecific findings.
B.Evidence of arterial thrombosis may manifest in signs of stroke, myocardial infarction, DVT, PE, or digital ischemia.
C.Skin necrosis is associated with warfarin therapy.
Diagnostic Tests
A.Complete blood count (CBC).
B.Prothrombin time.
C.Activated partial thromboplastin time.
D.Antiphospholipid antibodies.
E.Protein C—may be low in acute thrombosis.
F.Protein S—may be low in acute thrombosis.
G.Antithrombin III—may be low in acute thrombosis.
Differential Diagnosis
A.Paroxysmal nocturnal hematuria.
B.Homocysteinemia.
C.Heparin-induced thrombocytopenia.
D.Atherosclerosis.
E.Sickle cell disease.
F.Myeloproliferative diseases.
Evaluation and Management Plan
A.General plan.
1.Not all thrombotic episodes are associated with hypercoagulable risk factors and not all individuals with risk factors develop thrombosis.
2.Workup for coagulopathy is indicated with the presence of idiopathic or recurrent VTE, VTE before the age of 40, VTE with strong family history, VTE in an atypical site, or warfarin-induced skin necrosis.
3.Treatment involves reducing or eliminating factors that lead to thrombosis.
B.Patient/family teaching points.
1.Women need to avoid oral contraceptives or hormone replacement therapy.
2.Patients may need to be treated with lifelong anticoagulation to prevent further clotting.
3.Patients must be instructed on how to manage bleeding diathesis if on anticoagulation agents.
C.Pharmacotherapy.
1.Acute events require treatment with anticoagulants including heparin, warfarin, and other agents.
2.Immune suppression may be needed in some cases when the condition is refractory to anticoagulants.
D.Discharge instruction.
1.Patients will need to follow-up with hematology.
2.Any dental procedures or surgical interventions must be done in conjunction with the patient’s primary care provider.
Follow-Up
A.Monitoring of anticoagulation therapy posthospitalization is critical to preventing recurrence.
B.Patients should be cautioned to avoid trauma while receiving anticoagulant therapy.
C.Patients with modifiable risk factors including tobacco use or use of estrogen-containing oral contraceptives should be counseled about their use.
Consultation/Referral
A.Consultation with a hematologist is critical in the diagnosis and management of patients with hypercoagulable disorders.
B.It is also important that laboratory testing is completed at a facility with experience in utilizing specialized tests.
Special/Geriatric Considerations
A.Aging is accompanied by increased risk of both arterial and venous thrombosis.
B.While mechanisms are not entirely clear, a number of coagulation factors, including Factors V, VII, VIII, IX, and von Willebrand factor (vWF), increase with aging. This coupled with other comorbid conditions such as malignancy and structural changes in vascular endothelium contribute to an increased risk for thrombosis in older adults.
C.Special consideration is given for the use of anticoagulation in older adults to minimize the risk for bleeding. Careful monitoring of vitamin K antagonists is necessary.
D.Use of direct oral anticoagulants (DOAs) may be an alternative in some cases.
E.Education and monitoring to decrease risk for falls and other forms of trauma are essential for older adults receiving anticoagulation therapy.
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