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2384 Part XIII: Transfusion Medicine Chapter 139: Preservation and Clinical Use of Platelets 2385

The Thrombocytopenic Patient on Anticoagulation Therapy Patients who have a CCI of less than 5 × 10 /L on at least two con-
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Anticoagulation itself does not slow the formation of the primary plate- secutive occasions are considered to be “refractory” to platelet transfu-
let plug, although a decrease in thrombin generation would slow acti- sions. As the platelet count of the product is not usually available to the
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vation of more platelets and clot stabilization. It is not known whether clinician, two sequential 1-hour platelet increments of 11 × 10 /L or less
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higher counts are more appropriate for patients on anticoagulation, and may also be used to indicate refractoriness. Platelet refractoriness can
if so what the appropriate level would be. Although platelet counts of 40 be classified as immune or nonimmunologically mediated with the latter
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to 50 × 10 /L are often considered to be a safe level for patients antico- being the most common cause of platelet refractoriness. Unfortunately,
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agulated with warfarin or heparin therapy, there have been no trials to many patients concurrently experience both types of platelet refractori-
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evaluate whether lower counts would be as safe. ness. In the Trial to Reduce Alloimmunization to Platelets (TRAP) that
Platelet Transfusion Thresholds for Bleeding A paucity of evi- involved 533 patients given 6379 transfusions, the factors that most likely
dence exists on the target platelet count in bleeding patients. The site of resulted in platelet refractoriness, in order of frequency, were: develop-
bleeding and other hemostatic abnormalities or drugs that might result ing lymphocytotoxic antibodies; being female with two or more preg-
in a bleeding tendency should be considered and corrected as needed. nancies or male; heparin administration; fever; bleeding; transfusion
A target platelet count of 100 × 10 /L should be used in life threatening of γ-irradiated platelets; and receiving an increasing number of platelet
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bleeding such as intracerebral bleeding or diffuse alveolar hemorrhage transfusions. In addition, platelets express ABO antigen on their surface
to minimize compromise of healthy tissue. For diffuse microvascular and occasionally patients with high anti-A agglutinin titers may benefit
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bleeding, a platelet count of 100 × 10 /L is also usually recommended, 22,34 from ABO-matched platelets. Similar factors are associated with poor
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but difficulties of obtaining timely results during massive hemorrhage platelet responses in many other platelet transfusion studies. 23,44,45
make the feasibility of this approach unrealistic in the field and in many Active bleeding or denuded endothelium may cause increased
trauma centers. Retrospective analysis of combat casualties requiring platelet consumption so that the incremental increase in platelet count
massive transfusion (>10 units in 24 hours) found a transfusion ratio of is decreased. Patients with reduced responses to transfused platelets
one AP platelet component to every 8 units of red blood cells to be asso- due to increased platelet consumption may benefit from more frequent
ciated with significantly improved survival at 24 hours and 30 days in transfusions. The use of very frequent or continuous (“drip”) platelet
combat casualties requiring a massive transfusion (MT) within 24 hours transfusions in patients with life-threatening bleeding is sometimes
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of injury. Equal ratios of plasma, platelets, and red blood cells, is an undertaken, although no trials of this mode of therapy have been
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essential element of the United States Department of Defense “Damage performed.
Control Resuscitation” clinical practice guideline for control of massive Patients who have been previously transfused or pregnant may fail
hemorrhage adopted in 2006. In the Pragmatic Randomized Optimal to increase their platelet count following transfusion as a consequence
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Platelet and Plasma Ratios (PROPPR) study, 680 patients at level 1 of human leukocyte antigen (HLA) antibodies directed against the
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trauma centers requiring massive transfusion were randomized to one class I HLA antigens on the platelet surface. Transfusion of leukocyte
of two standard transfusion ratio interventions: 1:1:1 or 1:1:2 (plasma: reduced cellular blood components can reduce the rate of formation
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platelets: red cells), the equivalent of one AP platelet to every 6 or 12 of these antibodies. A minority of patients will develop or recall these
units of red blood cells. Both 24-hour and 30-day mortality were signifi- antibodies and have only minimal or no increase in the platelet count
cantly improved when the numbers of platelets and plasma transfusions following transfusion. There are a number of methods for HLA anti-
were increased to a 1:1 ratio with red blood cell transfusions. 38 body testing, either by cell-based or solid-phase assays. Testing can be
used to screen for antibodies and to identify antibody specificity to aid
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The Bleeding Patient on Platelet Inhibitor Therapy in donor selection. The results of these assays are expressed as a per-
Although aspirin inhibits the production of thromboxane A , an effect centage of the test cells or beads that bind patient antibodies. Patients
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that lasts for days after ingestion, the drug itself has a relatively short with poor responses to platelet transfusions because of HLA antibodies
half-life of 2 to 3 hours, whereas other nonsteroidal antiplatelet agents may benefit from HLA-matched platelets, identifying the specificity of
have effects that last less than 24 hours. Thienopyridine-class anti- the patient’s antibodies and avoiding any incompatible antigens or using
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platelet agents such as clopidogrel have much longer half-lives, as do platelet crossmatching assays to select compatible donors. 43,48,49
the active metabolites of these drugs, and may continue to affect plate- In patients with marked splenomegaly, large doses of platelets may
lets for more than a week. Although it is common practice to transfuse increase the total body platelet mass and increase the platelet count.
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platelets to patients treated with these drugs if they suffer serious or Platelets are released from the spleen upon injection of epinephrine,
life-threatening bleeding, there are no data that have established the suggesting that under times of stress these sequestered platelets may
effectiveness of platelet transfusions in these patients. become available for hemostasis. Homologous platelets transfused to
patients with immune thrombocytopenia survive only a few hours in
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the majority of patients studied. Therefore, transfusion of platelets to
MANAGEMENT OF PATIENTS REFRACTORY patients with immune thrombocytopenia is appropriate only for life- or
TO PLATELET TRANSFUSIONS organ-threatening bleeding. Platelet transfusion was associated with an
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The incremental increase in platelet count following a platelet trans- increased risk of arterial thrombosis in patients with thrombotic throm-
fusion is dependent upon the platelet dose (number) and the patient’s bocytopenic purpura (TTP) and heparin-induced thrombocytopenia
blood volume (which is, in turn, dependent on their body size). The cor- (HIT), but not in patients with immune thrombocytopenia (ITP). 52
rected count increment (CCI), generally measured 30 minutes to 1 hour
following a platelet transfusion, takes into account both patient size and Use of Antifibrinolytic Therapy
the dose of platelets transfused and can be calculated by the formula: Tranexamic acid and aminocaproic acid improve bleeding and decrease
platelet use in patients with thrombocytopenia associated with hemato-
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logic malignancy. The use of antifibrinolytic therapy with tranexamic
(PosttransfusionPlateletCount −Pretransfusion Platelet Count) acid or -ε-aminocaproic acid has been suggested to augment other mea-
(BodySurface Area in Meters ) sures to decrease or prevent bleeding in patients who continue to bleed
2
CCI =
Number of PlateletsTransfused( ×10 ) in spite of platelet transfusions.
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