Match each patient's clinical and laboratory presentation with the specific underlying pathophysiological or molecular mechanism responsible for their hypercoagulable state.
- A 28-year-old pregnant woman is initiated on intravenous unfractionated heparin for a deep vein thrombosis; however, her activated partial thromboplastin time (aPTT) fails to prolong into the therapeutic range despite escalating doses.Decreased availability of a serine protease inhibitor, resulting in the inability of a heavily sulfated glycosaminoglycan to exert its catalytic therapeutic effect.
- A 35-year-old man with unprovoked pulmonary embolism has a normal baseline aPTT that fails to prolong appropriately in vitro upon the addition of a purified, activated vitamin K-dependent endogenous anticoagulant.A missense mutation replacing arginine with glutamine, which eliminates a critical regulatory cleavage site for an endogenous protease complex.
- A 30-year-old woman with recurrent second-trimester fetal loss presents with an isolated, prolonged aPTT that does not correct when her plasma is mixed in a 1:1 ratio with normal pooled plasma.Presence of immunoglobulins targeting phospholipid-binding plasma proteins, which paradoxically prolongs in vitro clotting assays while promoting in vivo thrombosis.
- A 42-year-old man with a family history of unprovoked venous thromboembolism is found to have significantly elevated baseline plasma levels of Factor II without evidence of an acute phase reaction.A nucleotide transition in the 3'-untranslated region of a coagulation gene mRNA, leading to increased stability and hyperproduction of the zymogen.
Cevap
The correct matches are: Heparin resistance matches with decreased serine protease inhibitor (Antithrombin deficiency); failure of aPTT to prolong with activated anticoagulant matches with the missense mutation eliminating a cleavage site (Factor V Leiden); prolonged aPTT not correcting on a mixing study matches with immunoglobulins targeting phospholipid-binding proteins (Lupus Anticoagulant); and elevated Factor II matches with the nucleotide transition in the 3'-UTR (Prothrombin G20210A).
Each clinical scenario distinctly isolates one classic hypercoagulable state. Heparin requires antithrombin (a serine protease inhibitor) to function. Factor V Leiden prevents cleavage by activated Protein C due to an amino acid substitution. Lupus anticoagulant (antiphospholipid syndrome) causes uncorrectable aPTT prolongation in vitro due to antibodies. The Prothrombin G20210A mutation increases mRNA translation, elevating Factor II levels.
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Anahtar Kavram
Understanding the precise molecular pathophysiology and resulting laboratory profiles of the primary inherited and acquired thrombophilias.