Pulmonary embolism and Von Willebrand disease.

Patients with Von Willebrand disease (VWD) often require desmopressin (DDAVP) or concentrate therapy prior to undergoing surgical procedures. Venous thrombosis following treatment with high purity factor VIII/VWF concentrate has been described. However, such complication after desmopressin therapy is extremely rare. We report a patient who developed pulmonary embolism after DDAVP therapy. A 34-year-old white woman complained of sudden onset shortness of breath and right sided pleuritic chest pain a few hours after an arthroscopic knee surgery for a torn meniscus of left knee. Her past medical history was significant for VWD, mild asthma and hypothyroidism. Prior to the arthroscopic procedure she was given DDAVP. Physical examination revealed a well-built woman in mild respiratory distress but with stable vital signs. Oxygen saturation was 95% on room air. Systemic examination showed bilateral basal crackles at the posterior lung fields, normal heart sounds, and mildly swollen left knee without any clinical signs of deep venous thrombosis. ABG showed an A-a gradient of 74. CBC, SMA-7, PT/INR, PTT, and BT were unremarkable. Venogram of lower extremities was negative for deep venous thrombosis. High resolution CT scan of chest showed an embolus at the bifurcation of the right main pulmonary artery. No other identifiable risk factors for venous thrombosis were found. She was anticoagulated with intravenous heparin, and discharged on therapeutic doses of coumadin. Though thrombotic events have been commonly reported with factor XI and factor VIII concentrates, it is an unusual complication after administration of DDAVP alone in a patient with VWD. DDAVP produces hemostatic effects by increasing the plasma levels of coagulation factor VIII and VWF. Review of the literature showed only one prior case report of pulmonary embolism in a patient with VWD after receiving DDAVP. However, unlike our patient, she had other risk factors for venous thrombosis. Post DDVAP therapy, large VWF pro-coagulant multimers are released. VWF-cleaving protease, a proteolytic enzyme that regulates VWF's physiologic activity, decreases post DDAVP therapy in an attempt to cleave the large multimers. This leaves a window period where the multimers are predominant thus producing a pro-coagulant effect that potentially could lead to a thrombotic event. In addition DDAVP raises levels of factor VIII: C (coagulant) released as an acute phase reactant thus contributing to the hemostatic process. In summary we hypothesize that the consumption of the enzyme after desmopressin induced release of VWF multimers lead to the pro-coagulant environment.

Sobia Ali, MD, Saima Ansari, MD, and Rakesh Shrivastava, MD. Unity Health System, Parkridge Hospital, Rochester, NY.