Page 2189 - Hematology_ Basic Principles and Practice ( PDFDrive )

1942 Part XII Hemostasis and Thrombosis

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circulating platelets. In addition to portal hypertension and Another surgical cause of platelet dysfunction relates to the use of
esophageal varices, this finding raises the possibility that localized deep hypothermic circulatory arrest in some surgeries. This procedure
vascular bed factors (including increased prostacyclin) may contribute involves cooling the vital organs to temperatures between 15°C and
to variceal bleeding. 22°C (59°F and 71.6°F) for reducing oxygen requirements of major
Because patients with cirrhosis often have a complicated hemo- organs such as the heart, brain, and kidney. 265
static picture that includes thrombocytopenia, decreased fibrinogen In patients with mechanical circulatory support such as LVADs
levels, and prolonged prothrombin and aPTTs, one might expect this or ECMO, continuous exposure of blood to nonbiological surfaces
to uniformly produce a severe bleeding diathesis. However, recent creates additional hemostatic problems. 266,267 Continuously elevated
studies have shown that the hemostatic defects in these patients are shear stress both elongates and breaks down vWF multimers mechani-
at least partially compensated through several mechanisms. The cally and facilitates the cleavage of high-molecular-weight vWF
potential to bleed because of thrombocytopenia is reduced because multimers by ADAMTS13, causing acquired von Willebrand
267
vWF levels are often elevated and ADAMTS13 activity is disease. Increased shear stress created by these devices also causes
decreased, 251–253 perhaps as a consequence of decreased synthesis by platelet receptor shedding. In a study evaluating patients with ECMO
hepatic stellate cells. The decreased concentrations of procoagulant and continuous flow LVADs, platelet surface receptor shedding was
factors are balanced by the decreased concentrations of anticoagulant demonstrated by elevated soluble GPVI levels in plasma, and signifi-
254
proteins. Dysfibrinogenemia produces a less severe hemostatic cantly reduced expression of GPVI and GP Ibα on the platelet
defect because of decreased plasminogen levels. 255,256 This balance surface. 268
may easily be tipped in either direction, favoring either bleeding or
thrombosis.
Although patients with cirrhosis may have platelet dysfunction, it MISCELLANEOUS
is usually not associated with serious bleeding. Bleeding in these
patients cannot be predicted with routine diagnostic tests, such as the Hypothermia
platelet count and bleeding time. 257,258
Hypothermia is defined as core body temperature below 35°C or
PLATELET DYSFUNCTION RELATED WITH 95°F and is classified as mild (32–35°C or 90–95°F), moderate
(28–32°C or 82–90°F), severe (20–28°C or 68–82°F), and profound
EXTRACORPOREAL CIRCUITS (below 20°C or 68°F). Major causes of hypothermia are exposure to
cold weather or immersion in cold water, but hypothermia can also
Extracorporeal circuits such as cardiopulmonary bypass (CPB), be caused by dehydration, severe trauma, massive transfusion, head
extracorporeal membrane oxygenation (ECMO), continuous flow injury, burns, sepsis, and drugs (e.g., alcohol, sedatives, and hypnot-
left ventricular assist devices (LVADs), and total artificial heart gener- ics). Age is an important risk factor because elderly adults and new-
ate high shear stress and affect blood cells, endothelial cells, and borns are particularly prone to hypothermia. Hypothermia is also
plasma proteins. intentionally induced in some cardiac operations. 265
Bleeding complications can be seen in 10%–20% of the patients Mild hypothermia is usually well tolerated, but mortality increases
undergoing CPB, and hemostatic disturbances are responsible from when the core body temperature falls below 20°C. In animals,
bleeding in nearly half of those patients. 259,260 CPB activates both hypothermia causes thrombocytopenia because of platelet sequestra-
coagulation and fibrinolytic systems, and causes consumption coagu- tion in the spleen and liver. Hypothermia inhibits platelet aggregation
lopathy. Besides the surgery itself, high shear stress and exposure of in response to thrombin and thromboxane, increases platelet expres-
the blood to artificial surfaces activates FXII and FXI directly, and sion of P-selectin, and decreases expression of the GPIb-IX-V
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induces blood cells to express TF. 259,261 complex. Both the thrombocytopenia and the functional defects
Typical findings after bypass surgery include a prolonged bleeding are reversible, returning to normal when the body temperature
time (longer than expected for the degree of thrombocytopenia), normalizes. 265
decreased platelet aggregation, decreased platelet agglutination in
response to ristocetin, and depletion of platelet α-granule and dense
granule contents. 262 ANTIPLATELET ANTIBODIES
As with hemodialysis, the platelet defect caused by CPB is most
likely a consequence of platelet activation and fragmentation within Immunoglobulins can bind to platelets in a specific or nonspecific
the extracorporeal circuit. The severity of the platelet abnormalities fashion and can disrupt platelet function. In conditions such as
260
correlates with the duration of the bypass procedure. With uncom- immune thrombocytopenic purpura (ITP), systemic lupus erythema-
plicated surgery, platelet function returns to normal within 24 hours; tosus (SLE), and platelet alloimmunization, the antibodies can trigger
however, a much longer time may be required in some patients, accelerated platelet destruction and subsequent thrombocytopenia.
and the platelet count typically does not return to normal for Surviving platelets, known as stress platelets, display enhanced func-
270
several days. 263 tion. Indeed, bleeding times in ITP may be shorter than expected
Thrombocytopenia is caused by hemodilution and deposition of for the degree of thrombocytopenia. Sometimes, however, the hemor-
platelets on the bypass circuit and, to a lesser extent, sequestration of rhagic tendency is out of proportion to the degree of thrombocyto-
damaged platelets in the liver. Platelet dysfunction during bypass may penia or persists after the platelet count returns to normal, suggesting
be caused by reversible adhesion and aggregation of platelets on that the bound antibody is perturbing platelet function. 271
fibrinogen adsorbed from plasma onto the bypass circuit material, In some patients with ITP or SLE, platelet dysfunction may be
mechanical trauma and shear stress, cardiotomy suction, trace con- suspected because mucocutaneous bleeding symptoms occur despite
centrations of circulating thrombin and ADP, complement activation, platelet counts that are usually sufficient for normal hemostasis
hypothermia, blood conservation devices; bypass priming solutions; (>50,000/µL), and the bleeding time may be longer than expected
and, with bubble oxygenators, exposure of platelets to the blood–air for the degree of thrombocytopenia. Patients with antiplatelet anti-
interface. 173,259 CPB consistently induces the formation of platelet bodies can exhibit defective platelet function in vitro even if they do
fragments, or membrane “microparticles,” evidence that the platelet not have prolonged bleeding times or clinical symptoms of excessive
surface membrane is subjected to severe mechanical stress and activa- bleeding, a situation similar to what occurs with aspirin ingestion or
264
tion during the procedure. Thus considerable platelet activation renal disease. For example, in two studies, 13 of 19 patients with ITP
and aggregation occur during CPB, which leads to deleterious effects demonstrated impaired platelet aggregation to ADP, epinephrine, or
from substances released from the platelets and the new adhesive collagen. 272,273 In two other studies, 22 of 35 patients with SLE were
molecules exposed on their surfaces, and renders the platelets rela- found to have decreased platelet aggregation in response to these
tively refractory to activation by agonists. agonists. 274,275 The platelet function abnormalities appear to be