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Zorluk: OrtaHemodynamic and Coagulation Processes

A 31-year-old woman comes to the office for preconception counseling. She has a history of two spontaneous abortions at 12 and 14 weeks of gestation. Three years ago, she developed a deep vein thrombosis in her left lower extremity following a minor ankle sprain. She currently takes no medications and has no other medical conditions. Vital signs and physical examination are unremarkable. Coagulation studies reveal a normal prothrombin time (PT) and a significantly prolonged activated partial thromboplastin time (aPTT). An aPTT mixing study is performed, and the patient's prolonged aPTT fails to correct after being mixed in a 1:1 ratio with normal pooled plasma. Which of the following best describes the underlying mechanism for this patient's abnormal laboratory finding?

  1. Interaction of autoantibodies with phospholipid-bound coagulation protein complexesCevap
  2. B
    Inherited resistance of a coagulation factor to degradation by activated protein C
  3. C
    Production of neutralizing autoantibodies directed specifically against coagulation factor VIII
  4. D
    Deficiency of a bridging glycoprotein that normally protects factor VIII from rapid clearance
  5. E
    Impaired gamma-carboxylation of glutamic acid residues on circulating coagulation factors

Cevap

The correct answer is the interaction of autoantibodies with phospholipid-bound coagulation protein complexes, which is the mechanism of the lupus anticoagulant.
This patient's history of recurrent fetal loss, unprovoked venous thrombosis, and an uncorrectable prolonged aPTT is diagnostic of antiphospholipid syndrome (APS). The abnormal lab finding is caused by the lupus anticoagulant, an antiphospholipid antibody. In vitro, these autoantibodies bind to the phospholipids used in the aPTT assay reagent, inhibiting the assembly of the prothrombinase complex and artifactually prolonging the clotting time. Because it is an antibody (inhibitor) rather than a missing factor, adding normal plasma does not correct the prolonged aPTT. Despite the prolonged clotting time in vitro, these antibodies induce a hypercoagulable state in vivo.

Adım Adım Çözüm

1
Analyze the patient's clinical history.
The patient has a history of recurrent fetal loss and an unprovoked deep vein thrombosis.
Identifying the pattern of thrombosis and pregnancy morbidity suggests antiphospholipid syndrome (APS).
2
Interpret the laboratory findings.
The patient has an isolated prolonged aPTT that does not correct with a 1:1 mixing study.
Failure to correct indicates the presence of a coagulation inhibitor (an antibody) rather than a factor deficiency.
3
Correlate the clinical syndrome with the laboratory inhibitor.
The inhibitor present is the lupus anticoagulant.
Lupus anticoagulant is an antiphospholipid antibody that is paradoxically prothrombotic in vivo but prolongs the aPTT in vitro.
4
Determine the molecular mechanism of the laboratory finding.
The lupus anticoagulant autoantibodies bind to the phospholipid surfaces used in the aPTT assay.
This binding prevents the assembly of the prothrombinase complex in the test tube, leading to an artifactual prolongation of the clotting time.

Anahtar Kavram

Antiphospholipid syndrome (APS) often presents with lupus anticoagulant, an autoantibody that prolongs the aPTT in vitro by binding to phospholipids, which fails to correct during a mixing study. In vivo, it causes a hypercoagulable state.
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Hemodynamic and Coagulation Processes

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