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Paroxysmal nocturnal hemoglobinuria is an acquired clonal stem cell disorder that results in abnormal sensitivity of the red blood cell membrane to lysis by complement The underlying cause is a defect in the gene for phosphatidylinositol class A (PIG-A), which results in a deficiency of the glycosylphos-

Moyo VM et al Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays Br J Haematol 2004 Jul;126(1):133 8 [PMID: 15198744] Parker C et al; International PNH Interest Group Diagnosis and management of paroxysmal nocturnal hemoglobinuria Blood 2005 Dec 1;106(12):3699 709 [PMID: 16051736]

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phatidylinositol (GPI) anchor for cellular membrane proteins In particular, the complement-regulating proteins CD55 and CD59 are deficient Paroxysmal nocturnal hemoglobinuria should be suspected in confusing cases of hemolytic anemia or pancytopenia The best screening test is flow cytometry to demonstrate deficiency of CD59 on red blood cells This test has largely replaced the classic sucrose hemolysis test





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Because most chunks of data are much larger than a single frame, they must be chopped up before they can be sent across a network When a serving computer receives a request for some data, it must be able to chop the requested data into chunks that will fit into a packet (and eventually into the NIC s frame), organize the packets for the benefit of the receiving system, and hand them to the NIC for sending The receiving system must be able to recognize a series of incoming packets as one data transmission, reassemble the packets correctly based on information included in the packets by the sending system, and verify that all the packets for that piece of data arrived in good shape This part is relatively simple the network protocol breaks up the data into packets and gives each packet some type of sequence number I like to compare this process to the one that my favorite international shipping company uses I receive boxes from UPS almost every day; in fact, some days I receive many, many boxes from UPS! To make sure I get all the boxes for one shipment, UPS puts a numbering system, like the one shown in Figure 2-36, on the label of each box A computer sending data on a network does the same thing Embedded into the data of each packet is a sequencing number By reading the sequencing numbers, the receiving system knows both the total number of packets and how to put them back together

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Classically, patients report episodic hemoglobinuria resulting in reddish brown urine Hemoglobinuria is most often noticed in the first morning urine, probably because of its increased concentration In addition to being prone to anemia, these patients are prone to thrombosis, especially mesenteric and hepatic vein thromboses Other common sites of thrombosis include the central nervous system (saggital vein) and the skin, with formation of painful nodules This hypercoagulopathy may be related to platelet activation by complement As this is a stem cell disorder, paroxysmal nocturnal hemoglobinuria may progress either to aplastic anemia, to myelodysplasia, or to acute myelogenous leukemia

X-linked recessive disorder seen commonly in American black men Episodic hemolysis in response to oxidant drugs or infection Minimally abnormal peripheral blood smear Reduced levels of glucose-6-phosphate dehydrogenase between hemolytic episodes

Anemia is of variable severity, and reticulocytosis may or may not be present Abnormalities on the blood smear are nondiagnostic and may include macro-ovalocytes Since the episodic hemolysis in paroxysmal nocturnal hemoglobinuria is intravascular, the finding of urine hemosiderin is a useful test Serum LDH is characteristically elevated Iron deficiency is commonly present and is related to chronic iron loss from hemoglobinuria, since hemolysis is primarily intravascular The white blood cell count and platelet count may be decreased A decreased leukocyte alkaline phosphatase evidence for a qualitative abnormality in the myeloid series may be seen Bone marrow morphology is variable and may show either generalized hypoplasia or erythroid hyperplasia Flow cytometric assays may confirm the diagnosis by demonstrating the absence of CD59

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