A 39-year-old woman with nephrotic syndrome presents to the emergency department with 1 week history of headaches and nausea. She develops an acute deterioration in her mental status and is intubated and mechanically ventilated. Imaging reveals cerebral venous sinus thrombosis of the sagittal and transverse sinuses. Heparin anticoagulation is prescribed; however activated partial thromboplastin time (aPTT) is 46 seconds after multiple boluses and infusion per hospital protocol.
Which of the following is the MOST appropriate next step in managing this patient’s condition?
Correct Answer: B
This patient’s resistance to heparin is likely because of an acquired antithrombin deficiency. Heparin resistance has been defined as a requirement of greater than 35 000 IU/d to achieve therapeutic anticoagulation. Nephrotic syndrome is one of the causes of acquired antithrombin deficiency. Antithrombin is a natural anticoagulant that inhibits thrombin, factor Xa, and other serine proteases. Heparin works by binding to antithrombin, causing a conformational change that results in a 1000-fold increase in the anticoagulant activity of antithrombin III (ATIII).
Hereditary antithrombin deficiency is very rare (1 in 5000 to 1 in 10 000). It is inherited in an autosomal dominant with variable penetrance. Patient’s with hereditary ATIII deficiency often have family members with a history of VTE. Acquired causes include acute thrombosis, liver disease, extracorporeal membrane oxygenation (ECMO), hemodialysis, and asparaginase therapy (treatment of acute lymphocytic leukemia). A functional antithrombin assay can help with the diagnosis of antithrombin deficiency.
Management options include transfusion with fresh frozen plasma (FFP, contains ATIII, which will allow heparin to exert its anticoagulant effect), infusion of ATIII concentrates, or using an alternative anticoagulant such as a direct thrombin inhibitor (bivalirudin).
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Which of the following is LEAST likely to be a manifestation of factor V Leiden?
Correct Answer: D
Factor V Leiden is a mutated form of coagulation factor V that results in resistance to the anticoagulant effects of protein C. As a result, individuals with this factor V mutation are at increased risk for VTE. Heterozygosity for factor V Leiden is the most common inherited thrombophilia in Caucasian individuals with VTE. Factor V Leiden should be considered in a patient presenting with VTE at a young age, VTE in an unusual location (eg portal vein, cerebral vein), or recurrent VTE. Diagnosis can be made by DNA analysis or a functional coagulation test for activated protein C resistance. There is data associating factor V Leiden mutation with superficial vein thrombosis, pulmonary embolism, cerebral vein thrombosis (especially in women taking the oral contraceptive pill), and portal or hepatic vein thrombosis. Current data associating factor V Leiden mutation with arterial thromboembolism is weak, and the effect is small, if present.
A 58-year-old obese man with pancreatic cancer recently started neoadjuvant chemotherapy before a planned surgical resection. He presents to the emergency department with shortness of breath and chest pain. His hemoglobin is 11.5 g/dL, platelets are 550 × 10 9 /L, and white blood cell count is 10.5 × 10 9 /L.
He is hemodynamically stable. He had noticed swelling of his left lower extremity a week prior. He denies family history of “clots.” Computed tomography (CT) angiogram revealed pulmonary embolism, and therapeutic anticoagulation is initiated.
Which of the following is a component of the Khorana score that has been validated as a risk factor for the development of venous thromboembolism (VTE) in a patient receiving chemotherapy?
Correct Answer: C
Cancer induces a hypercoagulable state that puts patients at risk for thrombotic complications. Up to 10% of patients with cancer may develop VTE. Certain tumor types are associated with higher risk: for example, 30% to 50% of patients with pancreatic cancer have evidence of thrombosis.
The Khorana risk score for VTE in cancer patients is a validated scoring tool intended to be used in patients undergoing chemotherapy to stratify patients in terms of their future risk of VTE. The tool can be used to identify patients who are high risk and select those patients for ultrasound screening to diagnose DVT early. Data regarding use of the score for selecting patients for thromboprophylaxis are pending.
Components of the score are:
A score of ≥3 infers a 6.7% to 7.1% risk of VTE in 2.5 months.
The combined oral contraceptive pill is associated with an increased risk of developing VTE.
Which of the following factors has been demonstrated to reduce the risk of VTE?
Correct Answer: A
VTE is the most common vascular complication of combined oral contraception (COC) use. Although the risk is higher than in nonusers, the absolute risk is low and much less than the risk of VTE in pregnancy and early postpartum.
Studies have demonstrated that the risk of VTE is reduced by use of lower doses of ethinyl estradiol (<50 µg) and second-generation progestins (levonorgestrel). The risk of VTE is actually highest in the first year of COC use. The risk of VTE rises sharply after the age of 39 years in women taking COC. Women who smoke also have a greater risk.
Which of the following laboratory findings is MOST likely to be found in a patient diagnosed with antiphospholipid syndrome?
Antiphospholipid syndrome is a systemic autoimmune disorder leading to a hypercoagulable state characterized by venous or arterial thrombosis in the presence of evidence of persistent antiphospholipid antibodies (anticardiolipin, anti-beta-2-glycoprotein, lupus anticoagulant). Antiphospholipid syndrome can occur as a primary condition or in the presence of another systemic autoimmune disease.
Diagnosis is made by a combination of clinical factors and laboratory tests:
Other laboratory findings include thrombocytopenia, prolonged aPTT in patients not receiving anticoagulation, and a history of false-positive serologic test for syphilis (antigen used in venereal disease research laboratory [VDRL] and rapid plasma reagin [RPR] tests contains cardiolipin). Leukocyte count and hemoglobin are not specifically associated with antiphospholipid syndrome.
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