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The PNH clone had increased to 67% suggesting a diagnosis of haemolysing PNH (figure 2) a condition which is strongly associated with both venous and arterial thromboembolic events

Posted on September 27, 2024 By scienzaunder18

The PNH clone had increased to 67% suggesting a diagnosis of haemolysing PNH (figure 2) a condition which is strongly associated with both venous and arterial thromboembolic events. Open in a separate window Figure 1 Coronary angiography. no intervention was performed and anticoagulation with heparin, aspirin and clopidogrel was initiated. At this point, potential causes of myocardial infarction with angiographically normal coronary arteries were considered.1 Echocardiographically, there was no evidence for a right-to-left shunt. The angiographic picture did not DO34 suggest vasospasms and the laboratory values showed no evidence for an inflammatory process. However, the patients medical history was remarkable for aplastic anaemia 9 years earlier, which had been successfully treated with two cycles of antithymocyte globuline and cyclosporine. Ever since, the patient was in a complete remission. However, 3 years prior to the current hospitalisation, flow cytometry demonstrated a small PNH clone, with 5% of granulocytes being fluorescein-labelled proaerolysin variant (FLAER)-negative. Anticoagulation was not initiated at that time because the PNH clone was small and because there were signs of haemolysis. Moreover, there was a medical history of no prior thromboembolic events. Unfortunately, the patient was lost to follow-up and flow cytometry could not be repeated. During the current hospitalisation, the patient presented with a Coombs-negative haemolytic anaemia (haemoglobin 93 g/l, reticulocyte count 160109/l, lactate dehydrogenase 2741 U/l, bilirubine 22 mmol/l, unmeasurably low haptoglobin) and a normal platelet count. The PNH clone had increased to 67% suggesting a diagnosis of haemolysing PNH (figure 2) a condition which is strongly associated with both venous and arterial thromboembolic events. Open in a separate window Figure 1 Coronary angiography. LAO/cranial view of the right coronary artery (RCA) showing distal thrombotic occlusion (arrowhead) of the posterolateral branch (PL). Open in a separate window Figure 2 PNH flow cytometry. Analysis from peripheral blood using a fluorescein-labelled proaerolysin variant DO34 (FLAER) that binds selectively to the GPI anchor allowing quantification of GPI expression on the cell surface. FSC and SSC denotes forward and sideward scatter. Primary gating on granulocytes, 67% of all granulocytes are FLAER-negative (PNH cells). Outcome and follow-up The patients further clinical course was complicated by a retroperitoneal haematoma and an aneurysm at the catheter insertion site. Anticoagulation was temporarily interrupted and DO34 the haematoma surgically evacuated. Two weeks later, the patient had to be readmitted with a non-ST-elevation myocardial infarction despite combination therapy with aspirin and a vitamin K antagonist with a subtherapeutic international normalised ratio (INR) level of 1.8 on admission. Because the patient remained haemodynamically stable and chest pain could be controlled conservatively we did not perform an emergency coronary angiography but intensified the antithrombotic treatment by adding unfractionated heparin. The following morning, the patient awoke with severe headaches. Laboratory values Calcrl at that time revealed a platelet count of 121 000109/l (150C450 000), an INR value of 2.6, a fibrinogen level of 4.4g/l (1.5C3) and a thrombin clotting time above the therapeutic range. The CT scan showed a massive intracerebral bleeding and an immediate neurosurgical intervention was performed. However, the patients neurological condition deteriorated rapidly and she died only few days later. Discussion PNH is a rare acquired disorder of haematopoietic stem cells primarily characterised by haemolytic anaemia and recurrent thromboembolic events.2 Pathogenetically, a mutation in the PIG-A gene leads to the loss of glycosylphosphatidylinositol (GPI) anchor proteins and the GPI-associated membrane proteins such as complement regulating proteins CD55 and CD59.3C5 This results in complement-mediated intravascular haemolysis. Recurrent thromboembolic complications are the hallmark of the disease and the leading cause of death among these patients. Although both DO34 venous and arterial thrombosis may occur, myocardial infarction due to thrombotic occlusions of coronary arteries is extremely rare accounting for less than 2% of all thromboembolic events.6 Like being constraint.

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