Journal of Clinical Apheresis 29:284–289 (2014)
Case Report Cocaine-Induced Microangiopathic Hemolytic Anemia Mimicking Idiopathic Thrombotic Thrombocytopenic Purpura: A Case Report and Review of the Literature Shelley Odronic,1 NurJehan Quraishy,1* Pooja Manroa,2 Yelena Kier,3 Anna Koo,4 Priscilla Figueroa,1 and Aaron Hamilton2 1
Section of Transfusion Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio 2 Department of Hospital Medicine, Medicine Institute, Cleveland Clinic, Cleveland, Ohio 3 American Red Cross Blood Services Northern, Ohio Region, Cleveland, Ohio 4 Section of Therapeutic Apheresis, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
Our understanding of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura (TTP) has increased, but remains incomplete, particularly with respect to cases of suspected TTP that are either unresponsive to therapeutic plasma exchange (TPE) or have normal ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) activity. A 53-year-old woman presented with severe anemia (hemoglobin 1.8 g/dL) and clinical and laboratory findings consistent with TTP in conjunction with acute cocaine use. The patient was treated with TPE until the pre-treatment ADAMTS13 activity was reported as normal without evidence of an inhibitor. TPE was stopped and the patient continued to improve without treatment. This patient’s microangiopathic hemolytic anemia (MAHA) appeared to be secondary to cocaine use. The proposed pathogenesis is likely a combination of cocaine-induced vasoconstriction, vascular damage, platelet activation, and procoagulation. This is the fifth published report of cocaine-induced MAHA and to our knowledge the first with ADAMTS13 C 2014 Wiley Periodicals, Inc. testing. J. Clin. Apheresis 29:284–289, 2014. V Key words: MAHA; TTP; plasmapheresis
INTRODUCTION
Microangiopathic hemolytic anemia (MAHA) occurs in a heterogeneous group of diseases and is characterized by mechanical destruction of red blood cells in the microvasculature resulting in schistocytes on the peripheral blood smear and other laboratory evidence of intravascular hemolysis. MAHA in association with thrombocytopenia is seen in thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP). TTP was originally described by Moschowitz in 1924 [1] and named by Singer et al. in 1947 [2]. Initially defined by the classic pentad of MAHA, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction, the modern diagnosis of TTP requires only the dyad of MAHA and thrombocytopenia in the absence of any other alternative clinically apparent etiology [3]. Our understanding of the pathogenesis of TTP has increased in the last several decades. Patients with TTP have an increase in circulating unusually large multimers of von Willebrand Factor (ULVWF) in their plasma [4] and the microthrombi in these patients are platelet-rich with abunC 2014 Wiley Periodicals, Inc. V
dant von Willebrand Factor (vWF) [5]. vWF is stored in Weibel–Palade bodies in endothelial cells and released into circulation as ULVWF, which have a high affinity for glycoprotein Ib-IX that is capable of inducing agglutination of circulating platelets spontaneously in the absence of sheer stress [6]. Sheer stress facilitates unraveling of ULVWF released from endothelial cells. Circulating ADAMTS13 is responsible for cleaving these ULVWF immediately after release into smaller vWF multimers that do not induce spontaneous platelet adhesion or agglutination [7,8]. Studies have demonstrated that idiopathic TTP, the most common form of TTP, is caused by inhibitors or proteolytic inactivators of ADAMTS13, primarily autoantibodies [7,8]. This results in a deficiency of *Correspondence to: NurJehan Quraishy, MD, Section of Transfusion Medicine, Cleveland Clinic Q6-2, 9500 Euclid Avenue, Cleveland, OH, USA. E-mail:[email protected] Received 13 September 2013; Accepted 27 December 2013 Published online 13 January 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21316
Cocaine-Induced MAHA Mimicking TTP TABLE I. Laboratory Values at Presentation Test Hemoglobin Platelet count PT INR aPTT Fibrinogen D-Dimer Serum creatinine BUN
Results
Reference Range
1.8 g/dL 40,000/mL 20.7 sec 1.9 33.8 sec 169 mg/dL 10150 ng/mL FEU 1.74 mg/dL 46 mg/dL
11.5–15.5 g/dL 150,000–400,000/mL 8.4–13.0 sec 0.8–1.2 23.0–32.4 sec 200–400 mg/dL 66%) and the inhibitor
Case Report Cocaine-Induced Microangiopathic Hemolytic Anemia Mimicking Idiopathic Thrombotic Thrombocytopenic Purpura: A Case Report and Review of the Literature Shelley Odronic,1 NurJehan Quraishy,1* Pooja Manroa,2 Yelena Kier,3 Anna Koo,4 Priscilla Figueroa,1 and Aaron Hamilton2 1
Section of Transfusion Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio 2 Department of Hospital Medicine, Medicine Institute, Cleveland Clinic, Cleveland, Ohio 3 American Red Cross Blood Services Northern, Ohio Region, Cleveland, Ohio 4 Section of Therapeutic Apheresis, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
Our understanding of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura (TTP) has increased, but remains incomplete, particularly with respect to cases of suspected TTP that are either unresponsive to therapeutic plasma exchange (TPE) or have normal ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) activity. A 53-year-old woman presented with severe anemia (hemoglobin 1.8 g/dL) and clinical and laboratory findings consistent with TTP in conjunction with acute cocaine use. The patient was treated with TPE until the pre-treatment ADAMTS13 activity was reported as normal without evidence of an inhibitor. TPE was stopped and the patient continued to improve without treatment. This patient’s microangiopathic hemolytic anemia (MAHA) appeared to be secondary to cocaine use. The proposed pathogenesis is likely a combination of cocaine-induced vasoconstriction, vascular damage, platelet activation, and procoagulation. This is the fifth published report of cocaine-induced MAHA and to our knowledge the first with ADAMTS13 C 2014 Wiley Periodicals, Inc. testing. J. Clin. Apheresis 29:284–289, 2014. V Key words: MAHA; TTP; plasmapheresis
INTRODUCTION
Microangiopathic hemolytic anemia (MAHA) occurs in a heterogeneous group of diseases and is characterized by mechanical destruction of red blood cells in the microvasculature resulting in schistocytes on the peripheral blood smear and other laboratory evidence of intravascular hemolysis. MAHA in association with thrombocytopenia is seen in thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP). TTP was originally described by Moschowitz in 1924 [1] and named by Singer et al. in 1947 [2]. Initially defined by the classic pentad of MAHA, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction, the modern diagnosis of TTP requires only the dyad of MAHA and thrombocytopenia in the absence of any other alternative clinically apparent etiology [3]. Our understanding of the pathogenesis of TTP has increased in the last several decades. Patients with TTP have an increase in circulating unusually large multimers of von Willebrand Factor (ULVWF) in their plasma [4] and the microthrombi in these patients are platelet-rich with abunC 2014 Wiley Periodicals, Inc. V
dant von Willebrand Factor (vWF) [5]. vWF is stored in Weibel–Palade bodies in endothelial cells and released into circulation as ULVWF, which have a high affinity for glycoprotein Ib-IX that is capable of inducing agglutination of circulating platelets spontaneously in the absence of sheer stress [6]. Sheer stress facilitates unraveling of ULVWF released from endothelial cells. Circulating ADAMTS13 is responsible for cleaving these ULVWF immediately after release into smaller vWF multimers that do not induce spontaneous platelet adhesion or agglutination [7,8]. Studies have demonstrated that idiopathic TTP, the most common form of TTP, is caused by inhibitors or proteolytic inactivators of ADAMTS13, primarily autoantibodies [7,8]. This results in a deficiency of *Correspondence to: NurJehan Quraishy, MD, Section of Transfusion Medicine, Cleveland Clinic Q6-2, 9500 Euclid Avenue, Cleveland, OH, USA. E-mail:[email protected] Received 13 September 2013; Accepted 27 December 2013 Published online 13 January 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21316
Cocaine-Induced MAHA Mimicking TTP TABLE I. Laboratory Values at Presentation Test Hemoglobin Platelet count PT INR aPTT Fibrinogen D-Dimer Serum creatinine BUN
Results
Reference Range
1.8 g/dL 40,000/mL 20.7 sec 1.9 33.8 sec 169 mg/dL 10150 ng/mL FEU 1.74 mg/dL 46 mg/dL
11.5–15.5 g/dL 150,000–400,000/mL 8.4–13.0 sec 0.8–1.2 23.0–32.4 sec 200–400 mg/dL 66%) and the inhibitor
