Silverstein and Hopper Chapter 105: Management of the Bleeding Patient in the ICU

What are the three pillars of patient blood management?

Detection and treatment of hemorrhage

Reduction in further blood loss

Harnessing patient specific physiologic reserves

How do primary hemostatic defects manifest?

Surface or mucosal bleeding

How do disorders of secondary hemostasis present?

Body cavity hemorrhage, hematomas, subcutaneous, intramuscular, or joint hemorrhage

Generalized Bleeding

Occurring in multiple parts of the body

Localized Bleeding

Confined to one particular area

Differentials for Hemorrhage

Disorders of primary or secondary hemostasis

Hyperfibrinolysis

Traumatic tissue damage

Intra- or postoperative complications

Rupture of mass lesions

DIC can result in uncontrolled severe bleeding, has a high mortality rate

• Most common cause of DIC in the ICU is sepsis

Common Acquired Primary Causes of Bleeding in the ICU

Immune-mediated thrombocytopenia

Bone marrow disease

Uremia

Hyperviscosity syndrome

Antiplatelet medications (clopidogrel)

Nonsteroidal antiinflammatory medications

DIC

Splenic Sequestration

Common Acquired Secondary Causes of Bleeding in the ICU

Liver failure

Anticoagulant medications (direct thrombin inhibitors, factor X inhibitors, warfarin)

Anticoagulant rodenticides

Consumptive processes

Extracorporeal therapies

Dilutional

Hypothermia (<34*C)

Acidemia (pH<7.2)

Hypocalcemia (ionized Ca <1 mmol/L)

Vitamin K1 deficiency

Common Causes of Fibrinolysis in the ICU

Acute traumatic coagulopathy

Liver disease

Neoplasia

Breed predisposition (Greyhounds)

Common Vascular Causes of Bleeding in the ICU

Infectious diseases (e.g. sepsis, rickettsial diseases)

Cushing’s disease

Hyperviscosity. syndromes

Drug-induced

Neoplasia

Trauma

Surgical bleeding

Ruptured Mass

Diagnostic Approach for Patients Exhibiting Cutaneous and Mucosal Bleeding

• Automated platelet count in conjunction with a blood smear is the first diagnostic test of choice to rule out a severe thrombocytopenia

• If platelet count is normal, platelet function testing can be performed

  • Requires fresh platelets that are tested ideally within 2.5 hours of collection

  • May not identify the specific reason for platelet dysfunction

• Buccal mucosal bleeding time could be considered as a simple bedside test of platelet function

  • Disadvantages

    • Operator dependent variability

    • Lack of ability to detect mild defects in platelet function

    • Unreliable prediction of surgical bleeding

• Platelet mapping viscoelastic test (VET) assays can quantify the degree of platelet dysfunction due to clopidogrel or aspirin administration

  • Insensitive for the diagnosis of platelet dysfunction and a severe decrease in platelet count and function must be present to affect the VET

Diagnostic Approach for Patients with Bleeding Consistent with Dysfunction of Secondary Hemostasis

Coagulation testing, consisting of activated clotting time (ACT), prothrombin time (PT), activated partial thromboplastin time (PTT), D-dimers, and VETs, should be considered

What results of coagulation testing are reflective of coagulopathy?

Prolonged clotting times >1.5-2 times the patient baseline or reference value

What is one of the most reliable predictors of massive transfusions in human patients?

An international normalized ratio (PT standardized to thromboplastin reagent) >1.5

What are prolongations of PT and PTT associated with in human and veterinary patients?

Blood loss and increased mortality

Sensitivity of Coagulation Tests

• Not much evidence that the standard plasma-based coagulation tests accurately reflect a clinical coagulopathy or are useful in guiding transfusion therapy in bleeding patients

• Standard coagulation tests are an insensitive indicator of clotting factor deficiency with 60-70% of the factor level decrease necessary for prolongation of PT and PTT

• ACT is less sensitive than PTT with less than 10% of factor activity necessary for the ACT prolongation

  • ACT, unlike PTT< may be affected by severe thrombocytopenia and may be increased in patients with platelet counts of less than 10,000/uL

• VET is a more sensitive diagnostic modality for identifying hemostatic abnormalities in bleeding patients

  • Advantage is its ability to evaluate the interaction of cellular components and coagulation factors, which is more indicative of in vivo hemostasis

  • VET-guided transfusion protocols have been documented to result in less blood product use, decreased morbidity, and possibly decreased mortality than protocols based on standard tests of hemostasis

• Imaging is useful for quantifying the degree and extent of the hemorrhage as well as identifying potential anatomic targets to address

What is the ideal resuscitative fluid for significant blood loss?

Whole fresh blood (WFB)

When is isotonic crystalloid therapy the recommended resuscitation fluid?

• Isotonic crystalloid therapy is the recommended resuscitation fluid for the initial treatment of patients suffering from hemorrhagic shock, especially when blood product therapy is not immediately accessible

  • Recommendations for resuscitation have recently shifted, with current guidelines favoring the administration of conservative volumes of crystalloids to avoid dilution of blood cells and coagulation factors, hypothermia, and acidosis, and to prevent formed clot dislodgement

What can be used for low volume fluid resuscitation?

Hypertonic saline

• May be a crystalloid of choice in polytrauma patients with suspected traumatic brain injury

Synthetic Colloids for Hemorrhagic Shock Resuscitation

Synthetic colloids have been used for hemorrhagic shock resuscitation but are not superior to crystalloids and can inhibit platelet function as well as induce a coagulopathy

Administration of Blood Products for Hemorrhagic Shock

• Administration of blood products in a 1:1:1 unit ratio of packed red blood cells (pRBCs):fresh frozen plasma (FFP): platelet concentrates, as well as additional fibrinogen concentrates in cases of severe hypofibrinogenemia, has proven beneficial in bleeding human trauma patients

  • This protocol has resulted in the lowest mortality rate when compared to other ratios

• No evidence for an ideal ratio in veterinary medicine

  • Fresh platelet concentrates are routinely not available so reasonable to use a combination of FFP and pRBCs

  • Consider high ratios of FFP to pRBCs on a volume basis in veterinary patients with active bleeding

Target Hematocrit/Hemoglobin

• Target hematocrit/hemoglobin concentration is controversial

  • Some recommend a higher hemoglobin threshold of 10 g/dl as a goal in actively bleeding humans and patients with comorbidities that may benefit from higher oxygen content

  • Conservative transfusion triggers that use a hemoglobin of 7 g/dl have been shown to be superior in some groups of bleeding patients

Hypotensive Resuscitation

• Strategy to minimize further blood loss and hemodilution from nonsanginous fluid administration

• Refers to maintaining mean arterial pressure (MAP) in the range of 60 mm Hg for up to 90 minutes

• Typically culminates in the definitive management of hemostasis with surgery

• TBI is a contraindication, must reestablish a MAP of 90 mmHg to preserve cerebral perfusion

Triad of Death

Acidemia + Hypothermia + Coagulopathy

How is the triad of death prevebted in bleeding ICU patients?

• Prevention achieved with special focus on active rewarming and refraining from the administration of large quantities of crystalloids which results in dilutional anemia and coagulopathy

• Correction of the underlying cause of acidemia should be attempted

  • Bicarbonate administration to correct acidemia has not been shown to improve outcome in acidemic, critically ill patients

Vitamin K for Control of Bleeding

• Intake may be inadequate and its absorption and recycling may be compromised in patients with intrahepatic and posthepatic cholestasis

• Administration at 0.5-1 mg/kg subcutaneously every 24 hours should be considered for coagulopathy associated with liver disease and biliary obstruction

Desmopressin (DDAVP) for Control of Bleeding

• Synthetic analog of L-arginine-vasopressin

• Most commonly used in bleeding patients to release von Willebrand factor and factor VIII from Weibel-Palade bodies in endothelial cells

• Enhances the density of platelet surface glycoprotein receptors, increasing their adhesion potential

• Dose of 1 mcg/kg subcutaneously should be considered in patients with evidence of platelet dysfunction

  • Could be repeated every 24 hours for up to 3 days, but there is about a 30% reduction in efficacy compared to initial administration

Antifibrinolytic Drugs for Control of Bleeding

• Currently the mainstays of treatment of patients with severe bleeding due to acute traumatic coagulopathy, liver disease, and surgical bleeding associated with a number of procedures

• Aminocaproic acid and tranexamic acid

  • Act by competitively inhibiting the lysine-binding sites on plasminogen, which prevents the conversion of plasminogen to plasmin in addition to direct inhibition of plasmin action

  • Higher doses might be needed in veterinary patients than in humans

  • In patients with severe traumatic hemorrhage, should be administered as soon as possible and preferably within 3 hours of the traumatic event