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.

5.4 Hemoglobin “Triggers”

• RBC transfusion in a dose-dependent manner is an independent predictor of mortality in critically ill adult trauma and surgical patients, despite pre-morbid 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 in ^{4 , 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.

5.6 Prophylaxis Thresholds

^{2 , 20 , 21 , 22}

See Table 5‑3.

5.7 Antiplatelet Reversal in Intracranial Hemorrhage

• Our institutional practice is to consider location and severity of bleeding, prior single versus dual antiplatelet use, and/or signs of early hematoma expansion and to target a goal of > 50,000/mm³ if transfusion is considered in this setting (see Fig. 5.1).

  • Consider goal of > 80,000 to 100,000/mm³ if undergoing neurosurgical procedures ^{20 , 21}

• No specific replacement strategy is recommended. Our institutional practice varies by antiplatelet agent:

  • Aspirin: 10 units of platelets, once

  • Clopidogrel, prasugrel, ticagrelor, ticlopidine: 10 units of platelets once but can be repeated every 8 hours until demonstration of radiographic stability of the hemorrhage for up to 48 hours

There is lack of strong evidence to support aggressive platelet transfusion. ¹⁸ Evidence from PATCH trial and other studies examined in the Neurocritical Care Society guidelines statement calls into question historical practice of transfusing platelets solely for prior antiplatelet use in the setting of spontaneous ICH and suggests that platelet transfusion for any antiplatelet agent or hemorrhage volume provides no clear benefit in those patients not undergoing neurosurgical procedure. ^{17 , 18 , 19 , 20 , 21 , 22}

5.8 Coagulation Cascade and Anticoagulants

(Fig. 5‑2)

• Arterial and venous thromboses are important causes of morbidity and mortality following brain injury.

• Prevention and treatment of thrombosis is an important consideration in the management of the neurocritical care patient.

• Indications may include ischemic stroke, carotid occlusion, cardiac thrombus, and pulmonary embolism (PE).

5.9 Anticoagulants

5.9.1 Warfarin

Indications

Wide range of thromboembolic, valvular, and cardiac disease states.

Dosing

Dosing is individualized and depends on:

• Hepatic impairment, nutritional state, age, cardiac function, risk for bleeding, genetic variants of CYP2C9 or VKORC1 enzymes, and concomitant use of enzyme-inducing medications

• Therapeutic international normalized ratio (INR) level generally is 2.0 to 3.0. Exceptions include 2.5 to 3.5 for mechanical mitral valve, mechanical aortic valve PLUS risk factors, and mechanical valve in aortic and mitral locations.

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1 Encephalopathy and Delirium 6 Cerebral Edema and Elevated Intracranial Pressure 9 Trauma 8 Treatment of Status Epilepticus in Adults 12 Brain Death in Adults 16 Pain Management in the Neuro-Intensive Care Unit (ICU)

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