Hypofibrinogenemia in Patient with Extended Exposure to Argatroban Therapy

A 42 year old female with past medical history of asthma and recent admission for Alprazolam overdose presented to our hospital with dyspnea and generalized weakness.. She was noted by paramedics to be hypoxic, hypotensive and bradycardic, and she was intubated in the field prior to arrival.. Medication prior to admission, Albuterol HFA. Patient had no known drug allergies. On presentation to the emergency department, patient appeared critically ill, hypotensive to 74/50 , hypoxic with oxygen saturation of 60%, heart rate of 137 BPM, respiratory rate 15/min, temp 99 F, and unresponsive to verbal stimuli. Endotrachial tube placement was confirmed using laryngoscope. Whilein ED, patient went into Pulseless Electrical activity state and CPR was started immediately. She was given one round of Epinephrine with return of spontaneous circulation after 3 minutes.

Bedside transthoracic echo suggestive of right heart strain, patient was given Tenecteplase given high risk of Pulmonary embolism. She was then transferred to the Intensive care unit and was started on pressure support.. Initial Chest CT angiogram showed no signs of pulmonary embolism. Pertinent laboratory values at admission were, serum Creatinine 1.28 mg/dl , WBC 14 K/mcl, HGB 12/4 g/dl, Platelet count 186 K/mcl, PT 12.4 sec, INR 1.1, APTT 29.9 sec, Arterial blood gas with PH 7.039, PCO2 70.9 mmhg, PO2 35.9 mmhg, HCO3 18.2 mmol/l and Lactate 11.0 mmol/l. Hepatic function panel showing Albumin 3.7 gm/dl, Total protein 7.2 gm/dl, Total Bilirubin 0.6 mg/dl, Direct Bilirubin 0.1 ml/dl, ALK Phos 95 U/L, ALT 58 U/L, AST 73 U/L.

Patient respiratory status improved and was extubated on day 2, she was transferred to step down unit. Patient initially was on DVT prophylaxis dose of LMWH 5000 unit at bed time. However on day 5 laboratory values were notable for a drop in Platelets to 37 K/mcl, suspicion that patient developed HIT as 4T score of 6 ( high probability of of HIT 64%) which was confirmed with positive Serotonin releasing essay. On day 6 post admission, patient reported right calf pain, venous duplex studyof the lower extremity was performed showing lack of compressibility in right proximal, middle and distal superficial femoral veins consistent deep venous thrombosis . A lung perfusion scan was done showing high probability of pulmonary thromboembolic process. Administration of Argatroban was initiated at 2 mcg/kg/min IV titrated to goal of APTT 1.5-3x of baseline up 100 sec. Subsequent daily labs showing continuous drop in Fibrinogen levels(persistent <35 mg/dl, Normal 233-394) with appropriate increase in APTT values ( therapeutic goal of 45-90) and normal PT, INR values.

Subsequently, patient was receiving fresh frozen plasma twice daily. After careful review of the case with hematology consult, the drop in Fibrinogen levels was noted to be corresponding with he 12 days of Argatroban administration, so decision was made to stop Argatroban and switch to fondaparinaux. Fibrinogen values returned to normal within 1 day of discontinuation of Argatroban therapy (bridging to W arfarin), raising the concern for Argatroban induced hypofibrinogenemia.