Platelet Transfusion Guidelines

The most common reasons for transfusing platelets are:

  • Decreased platelet production
  • Increased destruction
  • Qualitative platelet defects.

A high proportion of platelets are transfused prophylactically to reduce the risk of spontaneous bleeding in patients who are thrombocytopenic after chemotherapy or hematopoietic progenitor cell transplantation. AABB recently published updated guidelines for platelet transfusion (Kaufman RM, et al. Ann Intern Med. 2015;162(3):205-213. doi:10.7326/M14-1589).

Platelets should be transfused prophylactically to reduce the risk of spontaneous bleeding in hospitalized adult patients with therapy induced hypoproliferative thrombocytopenia when the platelet count is 10,000 cells/uL or less. Outpatients may be transfused at a higher threshold to reduce the number of clinic visits. In both clinical settings, a single unit of apheresis platelets is recommended, because studies have established that a higher dose does not provide additional benefit.

Because of the increased risk of hemorrhage, the National Comprehensive Cancer Network (NCCN) and the European Leukemia Net (ELN) have recommended higher transfusion thresholds for patients with acute promyelocytic leukemia (APL) than for other types of AML.  Prophylactic platelet transfusions are recommended when the platelet count falls below 50,000/uL in APL compared to 10,000/uL in other types of acute myelocytic leukemia (AML).

Serious bleeding complications after central venous catheter (CVC) placement are rare and often unrelated to platelet count. Prophylactic platelet transfusion is recommended for patients undergoing elective central venous catheter placement with a platelet count less than 20,000 cells/uL. This threshold also applies to placement of large bore catheters for apheresis in thrombocytopenic patients. AABB’s recommendation is lower than the 2012 Society of Interventional Radiology guideline which recommends a minimum platelet count of 50,000 cells/uL for CVC placement.

Bleeding complications with LP are rare, but CNS hemorrhage has the potential to cause devastating neurologic sequelae. Prophylactic platelet transfusion is recommended for patients having elective diagnostic lumbar puncture with a platelet count less than 50,000 cells/uL. A higher platelet count is often recommended for other procedures such as epidural anesthesia.

There is no evidence of increased perioperative risk bleeding risk in thrombocytopenic patients with platelet counts greater than 50,000 cells/uL and no evidence of coagulopathy. Prophylactic platelet transfusion should be reserved for patients having major elective nonneuraxial surgery with a platelet count less than 50,000 cells/uL. For neurosurgery, platelets are usually transfused prophylactically for a preprocedure platelet count below 100,000 cells/uL.

Prophylactic platelet transfusions are not recommended for patients with normal platelet counts who are undergoing cardiac surgery with cardiopulmonary bypass. Transfusion should be reserved for patients experiencing perioperative bleeding with evidence of thrombocytopenia or platelet dysfunction.

Antiplatelet medications are prescribed to prevent thrombosis in patients with coronary artery disease, stroke, transient ischemic attacks and peripheral arterial disease. When patients taking these medications develop bleeding or require an emergent invasive procedure, the antiplatelet effect needs to be rapidly reversed. Specific antidotes are not available. Randomized clinical trials have not been conducted and there are no evidence based guidelines. Five observational studies have not shown any benefit for transfusion of platelets receiving antiplatelet agents who present with traumatic brain injury.

The recent transfusion literature contains some recommendations for platelet transfusion therapy in these situations. The standard dose of aspirin varies from 81 to 325 mg per day. Aspirin is immediately absorbed after ingestion and irreversibly inhibits platelets within 15 to 30 minutes by binding to cyclooxygenase 1 (COX1). The half life of aspirin is 30 minutes. Aspirin has a low bleeding risk. Discontinuation of aspirin for 2 days will usually result in production of enough new platelets to provide adequate hemostasis for elective surgery. Aspirin effect on platelets can be assessed by platelet function testing on PFA-100. Aspirin effect includes a prolonged closure time with epinephrine and a normal closure time with ADP.

Dipyridamole (Persantin) inhibits 2,3 phosphodiesterase enzyme in platelets and inhibits ADP induced platelet aggregation. By itself, dipyridamole is considered to be a weak antiplatelet medication that seldom causes bleeding. Aggrenox is a more effective antiplatelet medication that is often prescribed for patients with a history of stroke. It is a combination of 25 mg aspirin and 200 mg of dipyridamole. Bleeding risk is low. Platelet transfusion is usually not necessary. The effect of dipyridamole can only be assessed by whole blood platelet aggregation.

Clopidogrel (Plavix) irreversibly inhibits platelet function by preventing binding of ADP to the platelet P2Y12 receptor. Clopidogrel is a prodrug which is metabolized to its active form by the cytochrome P450 enzyme pathway. A loading dose of clopidogrel (300-600 mg) inhibits platelet function within 2 to 4 hours, while a daily dose of 75 mg becomes effective within 24 hours and has maximum effect within 4 to 7 days. Circulating half life is 7 to 8 days.

Daily clopidogrel increases the risk of bleeding. Clopidogrel should be discontinued before elective surgery. At least 3 clinical practice guidelines provide direction regarding the timing of surgery in patients receiving Plavix. Each of these guidelines recommends discontinuing Plavix for at least 3 to 7 days prior to surgery to allow platelet function to return to normal and decrease the risk of bleeding.

  • The American College of Chest Physicians Evidence Based Clinical Practice Guidelines from 2008 state that platelet function returns to normal 7 days after the last dose of clopidogrel (Chest 2008;133:71S-105S, specifically page 217S)
  • The Society of Thoracic Surgeons Clinical Practice Guidelines, which were updated in 2011, state that previous reports recommended a 5 to 7 day delay after discontinuation of clopidogrel in patients requiring coronary artery bypass graft surgery to lessen bleeding (Ann Thorac Surg 2011;91:944-82, specifically page 951).
  • In between these two sets of guidelines is an update from May 2011 by the American College of Cardiology Foundation/American Heart Association for management of patients with unstable angina/non-ST elevation myocardial infarction. This document recommended withdrawing clopidogrel for at least 5 days prior to coronary artery bypass graft surgery (JACC 2011;57:1920-59).

All of these recommendations are based on the pharmacokinetics of clopidogrel and do not take into account individualized response to drugs. Approximately 40% of patients have suboptimal antiplatelet response to clopidogrel. Patients who are hyporesponders or nonresponders would be expected to normalize platelet function even sooner than 5 to 7 days after discontinuing clopidogrel. In our experience more than 50% of patients have <30% platelet inhibition within 3 days after discontinuing clopidogrel. An individual’s response to clopidogrel can only be determined by performing platelet function testing with the VerifyNow assay. Assessing P2Y12 inhibition with this assay may allow elective surgery to be performed sooner.

The PATCH trial was a multicenter randomized trial that investigated the effectiveness of platelet transfusion for patients on antiplatelet medications who developed intracranial hemorrhage (ICH). Antiplatelet medications included aspirin alone, aspirin plus dipyridamole, clopidogrel alone and aspirin plus clopidogrel. Patients transfused with platelets had more adverse events during their hospital stay and a higher mortality rate.

Platelet transfusion seemed inferior to standard care for patients who develop intracranial hemorrhage while taking antiplatelet therapy. Platelet transfusion is not recommended for these patients (Lancet 2016; 387:2605-13). 

Like clopidogrel, prasugrel (Efient) is also irreversibly inhibits binding of ADP to the platelet P2Y12 receptor. It is a prodrug which is metabolized to its active form by the cytochrome P450 enzyme pathway. Prasugrel is given as a loading dose of 60 mg followed by daily doses of 10 mg for patients weighing more than 60 kg. The daily dose is reduced to 5 mg per day for patients weighing less. Onset of action and circulating half life are similar to clopidogrel.

Prasugrel has a higher bleeding risk than clopidogrel. Prasugrel should be discontinued for 5 to 7 days before elective surgery. Platelet function can be assessed with the VerifyNow assay. One dose of apheresis platelets may be needed for bleeding or urgent surgery.

Patients undergoing percutaneous coronary intervention may be treated with platelet glycoprotein IIb/IIIa inhibitors (GpIIb/IIIa) such as Reopro, Integrilin and Aggrastat to prevent thrombosis. The platelet binding characteristics of these medications are summarized in the following table.

  Abciximab Eptifibatide Tirofiban
Brand Name ReoPro Integrilin Aggrastat
Structure Fab Ig Peptide Peptide
Plasma half life 20-30 minutes 2.5 hours 1.5 hours
Receptor half life 24-48 hours 2-4 hours 2-6 hours

All of these drugs have an immediate onset of action. Although abciximab is rapidly cleared from plasma, platelet aggregation may be inhibited for 36 hours after discontinuation of the infusion. Platelet aggregation returns to normal within 2 to 6 hours after discontinuation of eptifibatide or tirofiban. If bleeding occurs, infusion of the GPIIb/IIIa inhibitor should be immediately stopped for 30 to 120 minutes. In the event of serious hemorrhaging or emergent surgery, one or two units of single donor platelets may be necessary.

Selective serotonin reuptake inhibitors, such as fluoxetine, sertraline, paroxetine, and clomipramine, decrease the uptake of serotonin by platelets. Since platelets are unable to synthesize serotonin, these medications lower the intracellular serotonin concentration, inhibit platelet aggregation and increase the risk of abnormal bleeding including menorrhagia, metorrhagia, upper GI hemorrhage, cerebral hemorrhage, hematuria, hemoptysis, hemarthrosis, and post-op bleeding. Platelet transfusions will probably not be effective in controlling bleeding until after these medications have been discontinued for several half-lives.

Cryoprecipitate transiently corrects uremic platelet defects. Reversal of a qualitative platelet defect requires 10 units of cryoprecipitate.Improvement in platelet function may not be evident for up to 4 hours and lasts approximately 24 hours. Repeat doses of cryoprecipitate are less beneficial.  Dialysis also corrects the uremic qualitative platelet defect. Thus, the use of cryoprecipitate to correct a qualitative platelet defect should be reserved for life-threatening hemorrhage or prior to an invasive procedure.

Platelet transfusions for patients with platelet consumptive disorders (TTP, HIT, and ITP) may be harmful. A recent study used the Nationwide Inpatient Sample database to evaluate in-hospital platelet transfusion practices and their association with thrombosis and in-hospital mortality. They reviewed 10,624 admissions with TTP, 6,332 with HIT; and 79,980 with ITP from 2007 till 2011. Platelet transfusions were documented in 10.1% of TTP, 7.1% of HIT, and 25.8% of ITP admissions. Platelet transfusions in TTP were associated with higher odds of arterial thrombosis (OR=5.8, 95% CI=1.3-26.6) and mortality (OR=2.0, 95% CI=1.3-3.0), but not venous thrombosis. Platelet transfusions in HIT were associated with higher odds of arterial thrombosis (OR=3.4, 95% CI=1.2-9.5) and mortality (OR=5.2, 95% CI=2.6-10.5) but not venous thrombosis. All relationships remained significant after adjusting for clinical severity and acuity. No associations were significant for ITP (Goel R, Blood. 2015 Jan 14. pii: blood-2014-10-605493).

References

Bracey AW. et al. How do we manage patients treated with antithrombotic therapy in the perioperative interval. Transfusion 2011; 51:2066-77.

Pandit TN and Sarode R. Blood component support in acquired coagulopathic conditions: Is there a method to the madness? Am J Hematol2012;87:S56-S62.

Sarode R. How do I transfuse platelets (PLTs) to reverse anti-PLT drug effect? Transfusion 2012;52:695-701.

Kaufman RM, et al. Platelet transfusion: A clinical practice guideline from AABB. Ann Intern Med. 2015;162(3):205-213. doi:10.7326/M14-1589.

Goel R, Ness PM, Takemoto CM, Krishnamurti L, King KE, Tobian AA. Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality. Blood. 2015 Jan 14. pii: blood-2014-10-605493.

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