Chapter 109. Disorders of Platelets and Vessel Wall (Part 8)

Hemolytic Uremic Syndrome HUS is a syndrome characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. It is seen predominantly in children and in most cases is preceded by an episode of diarrhea, often hemorrhagic in nature. Escherichia coli O157:H7 is the most frequent, although not only, etiologic serotype. HUS not associated with diarrhea (termed DHUS) is more heterogeneous in presentation and course. Some children who develop DHUS have been found to have mutations in genes encoding Factor H, a soluble complement regulator, and membrane cofactor protein that is mainly expressed in the kidney. ...
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Chapter 109. Disorders of Platelets and Vessel Wall (Part 8) Chapter 109. Disorders of Platelets and Vessel Wall (Part 8) Hemolytic Uremic Syndrome HUS is a syndrome characterized by acute renal failure, microangiopathichemolytic anemia, and thrombocytopenia. It is seen predominantly in children andin most cases is preceded by an episode of diarrhea, often hemorrhagic in nature.Escherichia coli O157:H7 is the most frequent, although not only, etiologicserotype. HUS not associated with diarrhea (termed DHUS) is more heterogeneousin presentation and course. Some children who develop DHUS have been found tohave mutations in genes encoding Factor H, a soluble complement regulator, andmembrane cofactor protein that is mainly expressed in the kidney. Hemolytic Uremic Syndrome: Treatment Treatment of HUS is primarily supportive. In D+HUS, many (~40%)children require at least some period of support with dialysis; however, the overallmortality is 1.5 million), usually seen in the setting of amyeloproliferative disorder, have an increased risk of bleeding. This appears to bedue, at least in part, to acquired von Willebrand disease (vWD) due to platelet-vWF adhesion and removal. Qualitative Disorders of Platelet Function Inherited Disorders of Platelet Function Inherited platelet function disorders are thought to be relatively rare,although the prevalence of mild disorders of platelet function is unclear, in partbecause our testing for such disorders is suboptimal. Rare qualitative disordersinclude the autosomal recessive disorders Glanzmanns thrombasthenia (absenceof the platelet GpIIbIIIa receptor) and Bernard Soulier syndrome (absence of theplatelet GpIb-IX-V receptor). Both are inherited in an autosomal recessive fashionand present with bleeding symptoms in childhood. Platelet storage pool disorder (SPD) is the classic autosomal dominantqualitative platelet disorder. This results from abnormalities of platelet granuleformation. It is also seen as a part of inherited disorders of granule formation, suchas Hermansky-Pudlak syndrome. Bleeding symptoms in SPD are variable butoften mild. The most common inherited disorders of platelet function are disordersthat prevent normal secretion of granule content. Few of the abnormalities havebeen dissected at the molecular level, but these are likely due to multipleabnormalities. They are usually described as secretion defects. Bleeding symptomsare usually mild in nature. Inherited Disorders of Platelet Dysfunction: Treatment Bleeding symptoms or prevention of bleeding in patients with severedysfunction frequently requires platelet transfusion. Care is taken to limit the riskof alloimmunization by limiting exposure and using prestorage leukodepletedplatelets for transfusion. Platelet disorders associated with milder bleedingsymptoms frequently respond to desmopressin [1-deamino-8-D-arginine vasopressin (DDAVP)]. DDAVP increases plasma vWF and FVIII levels;whether it also has a direct effect on platelet function is unknown. Particularly formucosal bleeding symptoms, antifibrinolytic therapy (epsilon-aminocaproic acidor tranexamic acid) is used alone or in conjunction with DDAVP or platelettherapy. Acquired Disorders of Platelet Function Acquired platelet dysfunction is common, usually due to medications,either intentionally, as with antiplatelet therapy, or unintentionally, as with highdose penicillins. Acquired platelet dysfunction occurs in uremia. This is likelymultifactorial, but the resultant effect is defective adhesion and activation. Theplatelet defect is improved most by dialysis, but may also be improved byincreasing the hematocrit to 27–32%, giving DDAVP (0.3 µg/kg), or use ofconjugated estrogens. Platelet dysfunction also occurs with cardiopulmonarybypass due to the effect of the artificial circuit on platelets, and bleedingsymptoms respond to platelet transfusion. Platelet dysfunction seen withunderlying hematologic disorders can result from nonspecific interference bycirculating paraproteins or intrinsic platelet defects in myeloproliferative andmyelodysplastic syndromes.