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2084 Part XII: Hemostasis and Thrombosis Chapter 121: Acquired Qualitative Platelet Disorders 2085

and a bleeding diathesis reminiscent of Glanzmann thrombasthe- bypass, but thrombocytopenia can occur within 5 minutes and often
nia. 479–482,486–489 Similarly, autoantibodies against GPIb and integrin α β does not nadir for the first few days. 507,509,510 The major factor respon-
2 1
have been detected that selectively inhibit ristocetin-induced platelet sible for thrombocytopenia is hemodilution from priming the pump
aggregation 490,491 and collagen-induced platelet aggregation, 492,493 respec- with colloid or crystalloid solutions, but it is often more profound than
tively. A patient with ITP has also been identified whose anti-GPVI can be accounted for by hemodilution alone. 509–511 Platelet adhesion
autoantibody produced GPVI shedding from the platelet surface and to artificial surfaces in the circuit has been demonstrated by scanning
512
platelets unresponsive to stimulation by collagen. 494 electron microscopy. The mechanism of this interaction is uncertain,
Besides interfering with platelet function, some autoantibodies can but it may be a result of the deposition of fibrinogen on the bypass cir-
activate platelets and induce aggregation and secretion in vitro. Such cuit and platelet adhesion mediated by integrin α β . Less-common
513
IIb 3
antibodies can activate platelets through immune complex binding to causes of thrombocytopenia during bypass are disseminated intravas-
platelet Fc receptors, by depositing sublytic quantities of the membrane cular coagulation, sequestration of damaged platelets in the liver, and
514
attack complex of complement (C5b-9) on the cell surface, or by bind- heparin-induced thrombocytopenia. Like antibodies against the
495
246
ing to a specific membrane antigen. The prototypic example of this complex of platelet factor 4 and heparin that are commonly detected
phenomenon is heparin-induced thrombocytopenia in which antibodies after bypass surgery and can be responsible for heparin-induced throm-
496
bound to neoepitopes exposed on the platelet factor 4 molecule by hepa- bocytopenia, antibodies against protamine and protamine/heparin
rin activate platelets after binding to platelet Fc receptors (Chap. 118). 496 complexes are commonly detected as well. 82,515,516 Such antibodies may
contribute to the thrombocytopenia and possibly to thromboembolic
Clinical Laboratory Features and Therapy events following cardiopulmonary bypass. 517
Platelet dysfunction should be suspected in any patient with ITP or SLE Qualitative platelet defects are the primary nonstructural hemo-
who has mucocutaneous bleeding with a platelet count that is not ordinar- static defects induced by the bypass circuit 508,518 and are manifest as
ily associated with bleeding (e.g., equal to or greater than approximately abnormal ex vivo platelet aggregation, decreased ristocetin-induced
30 × 10 /L). Likewise, this scenario has been described occasionally in platelet agglutination, deficiency of platelet α and δ granules, release
9
patients with Hodgkin disease, 347,480 non-Hodgkin lymphoma and mye- of soluble CD40 ligand, and the generation of platelet microparti-
loma, 497,498 and hairy cell leukemia. The clinical spectrum of autoim- cles. 507,509,510,519–522 The severity of these abnormalities correlates with the
499
523
mune platelet dysfunction may also include some individuals with “easy duration of extracorporeal bypass and they generally resolve within
bruising” and a normal platelet count. These patients may have ITP with 2 to 24 hours. 508
“compensated thrombocytolysis,” as a substantial proportion have circu- Bypass-induced defects in platelet function are likely caused
lating antiplatelet antibodies and large platelets. 500 by platelet activation and fragmentation, 521,524 hypothermia, contact
Patients with antiplatelet antibodies may exhibit defective platelet with fibrinogen-coated synthetic surfaces, contact with the blood–air
function in vitro, even if they do not manifest a prolonged bleeding time interface, cardiotomy suction and retransfusion of cardiotomy suc-
or excessive bleeding. These deficits include impaired platelet aggregation tion blood, and platelet exposure thrombin, plasmin, ADP, or com-
to ADP, epinephrine, and collagen, 501–504 as well as impaired adhesion to plement. 513,519,525–528 Drugs such as heparin, protamine, integrin α β
IIb 3
the subendothelial matrix. The most frequently reported abnormalities antagonists, and aspirin, as well as the production of fibrin degradation
20
are absence of platelet aggregation in response to low concentrations of products, can also impair platelet function. 126,529–531 Controversy exists
collagen and absence of the second wave of aggregation in response to about the significance of these defects in vivo. Some investigators sug-
ADP or epinephrine. This pattern is identical to that seen in individuals gest that the entire qualitative platelet defect is a result of the use of
529
with inherited storage pool disease. In fact, both ITP and SLE may be heparin during bypass and its inhibitory effect on thrombin activity ;
associated with an acquired form of storage pool disease manifested by however, this would not account for the bleeding diathesis that can exist
a reduced platelet content of dense- and α-granule components. 432,505 In hours after heparin reversal.
one report, platelets in ITP also exhibited an activation defect manifested Hyperfibrinolysis may also contribute to the bleeding diathe-
by impaired conversion of arachidonic acid to TXA . 2 506 sis associated with cardiopulmonary bypass. 532,533 This is likely from
Because antibody-mediated platelet dysfunction and bleeding thrombus formation in the pericardial cavity followed by local, and
532
almost always occur in the setting of ITP, therapeutic efforts should be subsequently systemic, fibrinolysis. The relevance of hyperfibrinoly-
directed to the treatment of these disorders. sis to postbypass bleeding is bolstered by the efficacy of antifibrinolytic
therapy in minimizing cardiopulmonary bypass surgery blood loss.
CARDIOPULMONARY BYPASS Therapy
Definition and History A preoperative evaluation of cardiac surgical candidates should include
Circulating blood through an extracorporeal bypass circuit during a history of bleeding in either the patient or family member. Some
cardiac surgery induces a variety of hemostatic defects. The most sig- authors recommend a screening prothrombin time, partial proth-
nificant of these are thrombocytopenia, platelet dysfunction, and hyper- rombin time, and bleeding time even in individuals with no history of
fibrinolysis. 507–509 At their extreme, these defects can result in substantial bleeding. However, the validity of this approach is controversial.
534
535
postoperative bleeding that may last hours to days after bypass. Approx- Regardless, prophylactic transfusion of allogeneic blood components
imately 5 percent of patients experience excessive postoperative bleed- is not indicated. 508,536,537 Preoperative administration of recombinant
ing after extracorporeal bypass; roughly half of the bleeding is from human EPO has been reported to reduce the need for allogeneic blood
surgical causes; much of the remainder is caused by qualitative platelet transfusion in undergoing elective open-heart surgery. 538–541 Cell savers
defects and hyperfibrinolysis. are now often used during bypass surgery and the collected washed
autologous red blood cells are reinfused after completion of cardiopul-
Etiology and Pathogenesis monary bypass. In addition, blood collected from chest tube drainage
Thrombocytopenia is a consistent feature of bypass surgery. 126,508 Typ- has been reinfused to minimize allogeneic transfusions. The safety of
541
ically, platelet counts begin to decrease to approximately 50 percent transfusing large quantities of blood by this technique has not fully been
of presurgical levels within the first half hour after the initiation of established. 528,542

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