Platelets: an update on diagnosis and management of thrombocytopenic disorders.
Thrombocytopenia in the pregnant patient may result from a number of causes, most of which involve either immune-mediated platelet destruction or platelet consumption. Many of these disorders share clinical and laboratory features, making accurate diagnosis difficult. Moreover, uterine evacuation is indicated in the therapy of some disorders, while in others alternative interventions may allow the pregnancy to be carried to term. These and other issues are discussed as part of a comprehensive review of the differential diagnosis and management of thrombocytopenia in pregnancy. The term "refractory ITP" is used with reference to two distinct groups of patients: 1) patients in whom the platelet count cannot be easily increased, including those who are poorly responsive to initial single agent treatment, and 2) those with persistent thrombocytopenia despite the use of conventional therapies. An approach to management of the former group will be presented, followed by a discussion of patients with chronic refractory ITP. The latter will include presentation of new data on the role of Helicobacter pylori in ITP and whether its treatment ameliorates thrombocytopenia, as well as the use of rituximab and other modalities. Thrombotic microangiopathies such as thrombotic thrombocytopenic purpura (TTP) are rare, but life threatening causes of thrombocytopenia. Ultra-large multimers of von Willebrand factor (vWF) aggregate platelets intravascularly, and congenital or immune-mediated deficiencies of a metalloprotease that cleaves these ultra-large multimers may cause TTP. However, little information exists concerning the behavior of this protease in other physiological and pathological conditions. Levels of this protease have now been measured in healthy individuals of different ages, full-term newborns, pregnant women and a patients with variety of pathologic conditions, and these data will be reviewed herein. Heparin-induced thrombocytopenia/thrombosis (HIT/T) remains the most common antibody-mediated, drug-induced thrombocytopenic disorder, and a leading cause of morbidity and mortality. Based on clinical correlations and murine models, there is increasing evidence that antibodies to complexes between platelet factor 4 (PF4) and heparin cause HIT/T, and the molecular composition of the relevant antigen has also become better defined. However, the introduction of sensitive ELISAs to measure anti-PF4/heparin antibodies has complicated diagnosis in some settings in which the incidence of such antibodies in unaffected patients exceeds the incidence of the disease. In addition, the FDA approval of Lepirudin and Argatroban has expanded the repertoire of agents available for therapy of HIT/T and may change the approach to management of asymptomatic patients with thrombocytopenia. However, the optimal use of these drugs in commonly encountered settings remains in evolution, and a need for alternative approaches to prevention and treatment is evident.
McCrae
K R
KR
Department of Hematology/Oncology, Case Western Reserve University, School of Medicine, Cleveland, OH 44107-4937, USA.
Bussel
J B
JB
Mannucci
P M
PM
Remuzzi
G
G
Cines
D B
DB
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000818:Animals; D001792:Blood Platelets / Q000473:pathology*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000201:enzymology / Q000209:etiology; D006493:Heparin / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D011696:Purpura, Thrombocytopenic / Q000209:etiology / Q000276:immunology / Q000628:therapy; D013921:Thrombocytopenia / Q000175:diagnosis / Q000209:etiology / Q000628:therapy
D006493:Heparin; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human