A 63-year-old Caucasian woman without medical history stayed for several weeks in Cameroun, without taking any antimalarial chemoprophylaxis. She developed severe gastrointestinal symptoms and, after three days, due to her suspicion of a malaria attack, she took at once four pills of Coartem (each containing 20 mg artemether and 120 mg lumefantrine). After that, the patient became unable to ingest any food or drug and a transfer to Europe was rapidly decided. She became seriously ill during the flight back. On arrival at the airport, she was found stuporous and hypotensive and was rapidly transferred to the intensive care unit (ICU) of the nearest hospital. The diagnosis of Plasmodium falciparum malaria was rapidly made on the blood smear and treatment was started with intravenous quinine and doxycycline (as artesunate was not available). Parasitemia was estimated less than 1%. Admission coagulation tests revealed activated partial thromboplastin time 37 sec, international normalized ratio 1.2, fibrinogen 299 mg/dL, D-dimers >8000 ng/mL (normal, <500), ADAMTS13 activity undetectable (reference range, 50–150%), von Willebrand factor (VWF) antigen 340% (reference range, 50–150%), and platelet count 21,000/mm³. Early complications included refractory hypotension and hypoxemia and neurological worsening. Intubation was required for mechanical ventilation; norepinephrine infusion was progressively increased to the maximal infusion rate of 46 μg/min. An acute left ventricular dysfunction could be demonstrated at echocardiography. Continuous venovenous hemofiltration was initiated for acute renal failure. Due to the evidence of multiple organ failure and despite relatively low parasitemia, exchange transfusion therapy was performed. Only one session of 87 minutes was performed. The patient's theoretical total blood volume was 4407 mL; on the whole, 1409 mL of red blood cells was removed and replaced by 1277 mL of packed red blood cells. Blood coagulation tests remained disturbed, with epistaxis and rectal bleeding. The nadir of platelet count (5,000/mm³) and plasma fibrinogen (66 mg/dL) was noted on day 4, but there was only a mild increase in activated partial thromboplastin time and prothrombin time. The activity of ADAMTS13 slightly increased to 32%; no inhibitor or ADAMTS13 autoantibodies were found. From day 2, blackish discoloration of both hands and feet was noted and by the following days a definite line of demarcation was observed between gangrenous and normal skin (). Ultrasound-Doppler examination confirmed the absence of distal perfusion. Plastic surgeon suggested postponing the extensive surgery. Further clinical course was characterized by repeated candidemia (days 4, 7, 9, 10, and 11) and bacteraemia (Pseudomonas aeruginosa on day 7 and Enterococcus faecalis on days 12, 13, and 18), despite appropriate antifungal and antimicrobial therapy. The abdomen computed tomography (CT) failed to reveal bowel ischemia, but diffuse thickening of the jejunal wall was found. Endoscopy on day 11 disclosed multiple duodenal ulcerations from ischemic origin (); colonoscopy performed on day 28 was also consistent with ischemic injury disseminated in the sigmoid colon (). Norepinephrine infusion had been definitely stopped on day 14. The patient regained consciousness progressively from day 22 and extubation was possible on day 32.\nThe decision to perform quadriamputation was discussed after recovery from the critical period, when she became able to give her consent. Surgery was performed two months after the first signs of peripheral gangrene. Renal function recovered and the patient was further transferred for rehabilitation.
A 54 years old male Ugandan presented to Kenyatta National Hospital, a major referral tertiary hospital, in Kenya. He had initially reported with headache and joint pain to a local health facility in Uganda and was diagnosed to have severe Plasmodium falciparum malaria infection, and thereafter treatment with intravenous quinine commenced.\nTreatment at the facility had been responsive; however two days after the onset, the patient started experiencing episodes of headache, pain, numbness, coldness, and swelling of the extremities. This was followed by darkening of the digits of his toes and hands, which gradually progressed proximally.\nOn presentation at out institution, he was conscious, alert, oriented, but lethargic and unable to walk. He was a non-smoker and non-alcoholic, and had no history of diabetes, hypertension or any angiopathies. He however had a history of numerous episodes of malaria bouts and a family history of hypertension with his father having succumbed to a stroke.\nOn physical examination, apart from fever, abdominal, cardiovascular, respiratory, and neurological systems were normal. Jaundice, pallor and cyanosis were absent. A right low paramedian scar was noted secondary to appendicectomy conducted in the year 1995. On local examination, the overlying skin cold, dry, wrinkled, and was darkened with a clear line of proximal demarcation (). Pain was present in the regions proximal to the discolouration, and absent in the distal regions.\nInvestigations tested negative for HIV, HBV, HCV, and VDRL on ELISA. Urea, Electrolyte and creatinine tests were normal. Clotting profile showed a prolonged Prothrombin time of 19sec, Prothrombin time index of 74%, and an INR of 1.36. A haemogram showed macrocytic normochromic anaemia (Hb 9.03 g/dL, MCV 89.9fL, MCH 29.5pg, MCHC 27.2g/dL), Hct 33.2%, RBC 3.69x1012/L. WBC 4.39x109, Neutrophils 2.11x109 (48.2%), Lymphocytes 1.73x109 (39.5%), Monocytes 0.314x109 (7.16%), Eosinophils 0.193x109 (4.4%), Basophils 0.035x109 (0.796%).\nAn echocardiogram was normal except for type 1 left ventricular dysfunction and mild tricuspid regurgitation. The Dorsalis pedis pulses showed absence of blood flow, and a diagnosis of Symmetrical peripheral gangrene was made. Management was initiated with clopidogrel, Acetylsalicylic Acid, and Atorvastatin, and quad-amputation recommended. Time was allowed for marginalization of the gangrene, which was noted two months later. Meanwhile fresh frozen plasma was regularly administered to counter suspected thrombophilia.\nFollowing satisfactory marginalization of the gangrene, the patient underwent surgical excision of the necrotic tissue. This involved transmetatarsal amputation of both feet and ray amputation of the hands. The wounds healed well thereafter facilitated by vacuum dressing at -7.5mmHg over one month. He was then referred to plastic surgeons for prosthesis.