Transfusion Medicine and Anticoagulation

5 Transfusion Medicine and Anticoagulation

Bhuvanesh Govind and Matthew Vibbert

Abstract

Anemia of critical illness, thromboses, and coagulopathies are common complications in the neurologic intensive care unit (ICU). A judicious approach that considers risks of therapy while optimizing tissue oxygen delivery, restoring homeostatic balance in coagulopathy, and treating arterial or venous thromboses should be pursued to improve outcomes. The chapter will discuss high-yield points in pertinent transfusion topics in the neurocritical care unit, including a review of the pharmacology and reversal of commonly encountered anticoagulant medications.

Keywords: transfusion, coagulopathy, anticoagulation, deep vein thrombosis, venous thromboembolism

5.1 Introduction

Anemia in critically ill patients is not uncommon. It has been estimated to occur in up to 95% of patients within 3 days of hospitalization.¹ Studies estimate that patients can lose between 40 and 60 mL/day through phlebotomy in the intensive care unit (ICU).¹ The etiology behind anemia is varied with some of the most common causes listed below. The decision to transfuse packed red blood cells (RBCs) in neurologically injured patients is often based on the underlying brain injury, indication for surgery, and optimization for cerebral metabolic demands.

5.2 Anemia in the ICU

• Defined as a reduction in RBC mass

• Mechanism of anemia is beyond the scope of this chapter, but etiology could be related to RBC production, survival, or destruction

• Common finding in many ICU patients is that it is often from a multifactorial etiology ²

◦ Bleeding

◦ Frequent phlebotomy

◦ Hemodilution secondary to fluid resuscitation

◦ Anemia of critical illness

– Reduced red cell production and survival

– Iron sequestration due to increased ferritin in acute inflammatory states

5.3 Red Cell Transfusion

One unit of packed red blood cell (PRBC) raises hemoglobin by 1 g/dL and hematocrit by 3% approximately. Most of the plasma component is removed and RBC component is mixed with about 100 mL of nutrient solution for extended storage life. Additional modifications considered include the following.

5.3.1 Leukocyte Reduction Indications

Reduction of febrile nonhemolytic transfusion reaction after multiple transfusions or in multiparous females, human leukocyte antigen (HLA) alloimmunization, or transfusion-related immunomodulation (TRIM) especially in postoperative patients.

5.3.2 Washed RBC

Reduction of severe allergic reactions, anaphylaxis in IgA deficiency.

5.3.3 Irradiation

Reduction of rare and fatal risk of transfusion-associated graft-versus-host disease (TA-GVHD) in certain at-risk populations such as neonates, patients with hematologic malignancies or stem cell transplants, or patients with congenital immune deficiency.

5.3.4 Complications of Red Blood Cell Transfusion

• Minor allergic reaction

• Acute or delayed hemolytic reaction

• Fever

• Transfusion-related acute lung injury (TRALI)

• Transfusion-associated circulatory overload (TACO)

• Transmission of viruses (hepatitis B virus [HBV], hepatitis B virus [HCV], human immunodeficiency virus [HIV])

• Increased risk of infection, pneumonia, and sepsis

5.3.5 Benefits to Transfusion

• Rapid volume expansion which is needed with acute blood loss. Symptoms of shock from blood loss do not usually manifest until a patient has lost approximately 1,500 mL of blood. ▶ Table 5.1 highlights the symptoms which can be found with acute blood loss.

• Increasing hemoglobin

5.4 Hemoglobin “Triggers”

• RBC transfusion in a dose-dependent manner is an independent predictor of mortality in critically ill adult trauma and surgical patients, despite premorbid level of anemia.¹⁴^,¹⁵^,¹⁶

• Trial of Transfusion Requirements in Critical Care (TRICC) defined universal hemoglobin goal of at least 7 mg/dL in critically ill patient.³

• Given that patients with primary neurologic injury were a small portion of the TRICC study population, concern exists that restrictive transfusion practices may not be generalizable in patients suffering severe brain injury, where signs and symptoms of tissue hypoxia may be difficult to detect.

• Moderate evidence exists to individualize hemoglobin goals based on specific disease states. Although there is no strong evidence toward suggesting significant improvement in outcomes, may consider transfusing for a liberalized goal of 8 to 10 mg/dL in⁴^,⁵^,⁶:

◦ Poor-grade subarachnoid hemorrhage (SAH)

◦ Large ischemic stroke (more than two-third of middle cerebral artery [MCA] territory)

◦ Severe traumatic brain injury

• Except in situations where a massive transfusion protocol is implemented, all transfusions should occur 1 unit at a time along with reassessment.

5.5 Thrombocytopenia

Thrombocytopenia is another major concern in the hospitalized patients and has been estimated to occur in upwards of 60% of ICU patients. In the critically ill patient, thrombocytopenia has been associated with a wide variety of causes. Trending the platelet count during the hospitalization is important and can lead to early recognition of life-threatening conditions such as heparin-induced thrombocytopenia (HIT). Common causes of thrombocytopenia include:

• Medications: ▶ Table 5.2 shows examples of specific medications

• Sepsis

• Disseminated intravascular coagulation (DIC)

• Acute respiratory distress syndrome

• Cardiopulmonary resuscitation (CPR)

• Massive bleeding

• Multifactorial

Either prophylactic transfusion for prevention of bleeding or treatment of active bleeding in specific scenarios must be utilized with fair consideration of the risks of transfusion.

• Risks are similar to those associated with red cell transfusion.

• Transfusion is not indicated in HIT, thrombotic thrombocytopenic purpura (TTP), or autoimmune thrombocytopenic purpura (ATP), unless significant bleeding occurs.

Table 5.2 Medications associated with thrombocytopenia

Antibiotics	Vancomycin, penicillin, trimethoprim-sulfamethoxazole, piperacillin
Anticonvulsants	Carbamazepine, phenytoin, valproic acid, levetiracetam
Anti-inflammatory	NSAIDs, naproxen, acetaminophen
Cardiovascular	Amiodarone, quinidine, furosemide, digoxin
H2 blockers	Famotidine, ranitidine, cimetidine
Other	Simvastatin, haloperidol, heparin, Lovenox, lithium
Abbreviation: NSAIDs, nonsteroidal anti-inflammatory drugs.

Table 5.3 Platelet transfusion goals for common procedures

Planned invasive procedure (lumbar puncture, CVC)	> 50,000/mm³ New limited data suggest thresholds for CVC placement can be as low as 20,000 mm;³ may be targeted if placement can be done safely with low risk of arterial puncture performed by an experienced operator¹⁹^,²²
Bronchoscopy with lavage (without biopsy)	> 20,000/mm³
Major surgery goals vary by situation and type of procedure (neurosurgical procedures may require higher goals):	> 50,000/mm³
Abbreviation: CVC, central venous catheter.

5.6 Prophylaxis Thresholds ²^,²⁰^,²¹^,²²

See ▶ Table 5.3.

5.6.1 Treatment of Bleeding

• Intracerebral hemorrhage with anticoagulant use (warfarin, oral Xa inhibitor, direct thrombin inhibitor): > 50,000/mm ³(institutional threshold)

• Current American Heart Association (AHA)/American Stroke Association (ASA) guidelines (2015) on spontaneous intracerebral hemorrhage (ICH) recommend that patients with severe thrombocytopenia should receive platelet replacement (Class IC recommendation),¹⁸ but it does not recommend at what threshold the platelets should be given or to what target.