Two patients exposed during surgery to bovine thrombin developed antibodies reacting with both bovine and human thrombin and Factor V. Their thrombin times were markedly prolonged with bovine thrombin and modestly prolonged with human thrombin. High titer anti-bovine Factor V created diagnostic confusion in one patient by neutralizing bovine Factor V in a prothrombin assay substrate. Although weaker, antibody activity against human Factor V led to postoperative factor V deficiency in both patients. Such cross-reacting antibodies, recognizable by their higher titer against bovine than human Factor V, should be suspected when a patient surgically exposed to bovine thrombin develops a Factor V anticoagulant after operation. Crossed immunoelectrophoresis of adsorbed bovine plasma with each patient's plasma as antibody revealed many precipitin arcs indicative of immunization of the patients to additional proteins in a commercial thrombin preparation.
Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by isolated overproduction of platelets, thrombohemorrhagic complications, and a median age of 50-60. When it occurs in younger patients, the incidence of complications has been reported to be quite low, with a good long-term prognosis. We report a retrospective review of 13 patients with ET between the ages of 22 and 35 in which 11 were symptomatic at diagnosis, with only one remaining asymptomatic during follow-up. Three patients presented with potentially life-threatening complications (two myocardial infarctions, one stroke), although no deaths were observed. The majority of the nonlife-threatening complications were vaso-occlusive in nature, including erythromelalgia and transient neurologic symptoms. We conclude that ET in young adults is not always a benign disease and that potentially life-threatening complications are not rare. The optimum approach to treatment in this or any other age group remains uncertain.
Platelets are heterogeneous in the content of membrane glycoprotein (GP)IIb/IIIa complex. To determine whether this heterogeneity is related to changes associated with platelet aging in the circulation, newly released platelets, obtained during recovery from nonimmune- mediated acute experimental thrombocytopenia in baboons, were studied. Monoclonal antibody (MoAb) binding to epitopes expressed on GPIIb/IIIa complex (LJ-CP8), GMP-140 (S12), and GPIa/IIa (12F1) was measured on control platelets (comprising platelets with a normal age distribution; mean age 60 to 72 hours) and newly formed platelets (mean age 12 hours), both in the resting state and after thrombin stimulation. Whereas LJ-CP8 binding to resting control platelets increased by 34% upon stimulation by gamma-thrombin from 30,885 +/- 1,171 to 41,458 +/- 1,311 molecules/platelet at saturating concentrations of antibody, LJ- CP8 binding to resting young platelets did not increase significantly upon thrombin stimulation (31,878 +/- 3,330 and 33,791 +/- 3,486 molecules/platelet, respectively). Similarly, binding of antibody S12 in response to maximal thrombin stimulation was reduced by 42% from 10,246 +/- 834 molecules/platelet at saturating concentrations of S12 for control platelets to 5,971 +/- 665 molecules/platelet for young platelets (P = .001). S12 binding to unstimulated platelets was less than 10% of the binding observed after thrombin stimulation at all concentrations of S12 for both control and young platelets. However, maximal binding of antibody 12F1 to resting control platelets did not differ significantly from that observed with resting young platelets (2,926 +/- 167 and 2,857 +/- 208 molecules/platelet, respectively), and 12F1 binding was unchanged after thrombin stimulation for both control and young platelets. We conclude that the thrombin-induced increase in the expression of epitopes on platelet membrane GPIIb/IIIa complex and GMP-140 is a function of platelet age.
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