A Case of Mistaken Identity: TTP-like State Due to Heroin Overdose

Learning Objective 1: Recognize that multiple etiologies can play a role in the overall presentation of patient's thrombocytopenia.

Learning Objective 2: Rethink the original working diagnosis when there is discordance with clinical picture.

Case: 52-year old male with a PMHx of heroin and alcohol abuse presented to ED after being found unresponsive due to heroin OD. Patient (Pt) was initially seen in the ED 4days prior for left leg cellulitis and was sent home on oral Bactrim. Lab values during that visit showed a platelet (plt) count of 80 K/UL, Hgb 10.1 g/dl and creatinine (Cr) of 1.46 mg/dl. On his 2nd ED visit, his WBC count was 12.7 K/UL, Hgb 7.7g/dl, plt 23K/UL, haptoglobin <8.0mg/dl and reticulocyte count of 4.1%. His BUN and Cr were elevated at 32 mg/dl and 2.97mg/dl respectively and UA showed large blood with 3-5 RBC, CPK was 24806 IU/L, LFTs demonstrated an AST of 414 IU/L, ALT of 90 IU/L, total bilirubin 2.0mg/dl, direct bilirubin 0.8mg/dl, LDH of 2339 IU/L and ESR >140 mm/hr. Coagulation parameters were normal. Pt's urine toxicology was positive for opiates and methadone. Manual differential was initially negative for schistocytes, helmet cells or bite cells. HIV was non-reactive, RPR and acute hepatitis panel were negative. On exam, pt was drowsy, had icteric sclera and faint left pedal pulses without purpuric rash. Pt was started on IV fluids for oliguric AKI and rhabdomyolysis. Arterial doppler revealed no detectable blood flow in his left distal superficial femoral, tibial and popliteal arteries. Initial CT head was negative for acute findings. Hematology consulted for possible diagnosis of TTP. Consultant didn't think clinical picture was consistent with TTP as total bilirubin at the time of consultation was normal therefore plasma exchange wasn't recommended. However, primary service still considered TTP highest on the differential therefore, ADAMTS13 was ordered but no plasma exchange was initiated. Given the fact pt received oral Bactrim for diagnosis of lower extremity cellulitis, G6PD deficiency was included in the differential however, testing was done early after hemolytic event and while reticulocytes were elevated, therefore results were not diagnostic. Of note, plts were transfused per vascular surgery prior to a planned thrombectomy of left leg, and plts increased to 81 K/UL. Pt underwent unsuccessful left leg thrombectomy due to chronic changes in the vessels and collaterals. CPK levels continued to increase and renal function continued to worsen as did his mental status. Pt was started on hemodialysis (HD) by end of 2nd day. There was persistent effort to incorporate all lab derangements into one all-inclusive diagnosis. Hematology was asked to review the case again as pt's plts continued to drop, ADAMTS13 activity was low at <2.0% and schistocytes were now noted on the peripheral smear. TTP was again not seen as the primary cause of the pt's clinical picture as total bilirubin continued to be normal, schistocytes only appeared after HD was initiated and low ADAMTS13 was thought to be secondary to liver dysfunction, inflammation and heroin OD. A repeat CT-head done showed left cerebellar hypodensities suspicious for acute CVA. Pt continued to deteriorate requiring mechanical ventilation. Troponins were checked which showed a level of 31.90ng/dl and ECG done simultaneously showed sinus tachycardia and no ischemic changes. Cardiology was consulted who determined trop elevation was likely due to skeletal muscle injury and possibly due to NSTEMI. However, due to pt's severe thrombocytopenia, Cardiology determined he was not a candidate for antiplatelet therapy or anticoagulation. Despite aggressive resuscitative measures, patient died

Discussion: We reviewed the literature to evaluate other causes of this pt's clinical picture. While pt has overlapping features of TTP except fever, other causes for his mild hemolytic anemia and low plts include polysubstance abuse, rhabdomyolysis, poor nutritional status, presence of alcoholic fatty liver and uremia. Thrombocytopenia is associated with an increased risk of adverse outcomes, regardless of the causes. It has been documented in literature that heroin OD can cause rhabdomyolysis, renal failure, cardiac dysfunction, and permanent neurologic complications. The original diagnosis of TTP was anchored on and we persisted in trying to make the clinical picture fit that diagnosis and delayed in looking at overall clinical picture of the pt.