a review on hematology and oncology emergencies

Hematology Hematology EmergenciesEmergenciesIntensive Course Final Year MMED Candidates 2009-2010

Chew Keng ShengSchool of Medical SciencesUNIVERSITI SAINS MALAYSIA

Whole BloodWhole BloodRarely used today (individual blood components provided separately)

Indications◦Autologous transfusion◦Exchange transfusion (ie, sickle cell anemia)

CommentsRisk of transfusion reaction is >2 times than with packed red blood cells (PRBCs)

Risk of allergic reaction is 1%

Packed Red Blood CellsPacked Red Blood CellsPreparationPlasma removed from whole blood and remaining RBC mass is washed

Washing RBCs removes leukocytes, platelets, proteins, and other antigenic components of whole blood

Type and cross-matchABO blood group antigen system and Rhesus system

Production of anti-D antibody occurs in Rh– individuals who have exposure to small amounts of D antigen

A) Maternal-fetal mixing (Rh– mother and Rh+ fetus)

B) Anti-D immunoglobulin required in Rh– mothers with exposure to D antigen within 72 hours of exposure

Packed Red Blood Cells Packed Red Blood Cells (2)(2)

IndicationsGenerally, transfusion is rarely indicated when Hb >10 g/dL and is almost always indicated in when Hb level < 6 g/dL

The determination of transfusion in patients whose Hb is 6-10 g/dL should be based on any ongoing indication of organ ischemia, the rate and magnitude of any potential or actual bleeding and the patient’s intravascular volume status.


IndicationsTransfusion for Hb >6 g/dL in healthy nonsurgical patients is generally not indicated because oxygen delivery in healthy adults is maintained even with Hb as low as 6-7 g/dL.

Transfusion usually recommended prior to major surgery when hemoglobin levels are <10 g/dL


IndicationsIn acute hemorrhage, up to 40% of the blood volume in a bleeding, otherwise healthy young adult can be replaced with crystalloid without the need for red cell transfusion.


CommentsEach unit of PRBCs has approximate volume of 250 mL

In adults, 1 unit of PRBCs increases Hb level by ~1 g/dL and hematocrit by ~ 3%

In children, PRBCs increase the hematocrit by 1% for each mL/kg transfused


Fresh Frozen PlasmaFresh Frozen PlasmaFrozen fluid product of centrifuged and separated whole blood

FFP is frozen at -18C or colder within 6-8h of collection

Contains normal plasma levels of stable clotting factors, albumin and immunoglobulin, but variably reduced levels of Factor V and Factor VIII

Before use, should be thawed in warm water which between 30°C to 37°C.

Higher temperatures will destroy clotting factors and proteins.

Once thawed, to be infused immediately (best within 6hr) or re-stored at 1-6C for up to 24 hours, which will be relabeled as Thawed Plasma, and to be used as a source of stable coagulation factors for up to 5 days

Fresh Frozen Plasma Fresh Frozen Plasma (2)(2)

IndicationsClotting factor deficiencies◦Hemophilia A◦Hemophilia B◦von Willebrand disease

Cirrhosis (lack factors II, VII, IX, and X)

Massive blood transfusion – may transfuse 1 unit of FFP for every 5 to 6 units of PRBCs

Coagulopathy secondary to super-therapeutic warfarin◦Transfusion of 5 to 10 mL/kg of FFP will reverse the effects of supertherapeutic warfarin


Requires ABO-compatibility; but not crossmatched

Amount to transfuse: 3 to 10 mL/kg or as needed

Each unit of FFP has a volume of ~200 to 250 mL

Each unit of FFP increases coagulation factor levels by 2% to 3%


CryoprecipitateCryoprecipitateCryoprecipitate prepared from precipitants of slowly thawed FFP between 1-6C. The cold insoluble precipitant then collected and refrozen within 1 hour.

Contains factor VIII, factor XIII, vWF, fibrinogen, and fibronectin

IndicationsHypofibrinogenemia (congenital, DIC, cancer,

CirrhosisReversal of tissue plasminogen activator

Coagulopathy from massive transfusion

Cryoprecipitate (2)Cryoprecipitate (2)

It is preferable to use cryoprecipitate that is ABO-compatible with the recipient’s red cells, but not crossmatched.

Infuse within 6 hours of thawing

Each bag of cryoprecipitate contains 10 to 25 mL of fluid

Cryoprecipitate (3)Cryoprecipitate (3)

PlateletsPlateletsObtained from centrifuged whole blood

IndicationsThrombocytopenia <10,000 cells/mm3 in asymptomatic patients

Thrombocytopenia <20,000 cells/mm3 with active hemorrhage

Thrombocytopenia <50,000 cells/mm3 undergoing invasive procedure

Dilutional thrombocytopenia (with massive blood transfusions)

Not indicated in diseases with ongoing consumption of platelets: ITP, TTP, untreated DIC & thrombocytopenia associated with septicaemia, until Rx has commenced or in cases of hypersplenism.

Platelets (2)Platelets (2)

Thienopyridine platelet ADP receptor inhibitors and direct glycoprotein IIb/IIIa inhibitors impair platelet function.

Platelets should not be transfused prophylactically without thrombocytopenia, but high dose therapeutic transfusion may be required for life threatening hemorrhage in patients on these drugs.


Amount to transfuse: 1 unit per 10 kg body weight (6 to 10 units of platelets for the average adult)

Cross-matching is unnecessary, but all transfused platelets should be ABO and Rh compatible

1 unit increases the platelet count by 5000 to 10,000 cells/mm3


COMPLICATIONS OF COMPLICATIONS OF TRANSFUSIONTRANSFUSION

Massive TransfusionMassive Transfusion

DefinitionNo strict definition but commonly referred as the replacement of entire body blood volume within 24 hours, or >10 units of PRBC transfusions within a few hours

ComplicationsMetabolic alkalosis and hypocalcemia secondary to citrated blood

Hyperkalemia or hypokalemiaHypothermiaDilutional coagulopathyThrombocytopeniaAcute respiratory distress syndrome (ARDS)

Massive Transfusion Massive Transfusion (2)(2)

Administer via blood warmer (no microwave)

Calcium gluconate (if ECG changes occur)

Massive Transfusion Massive Transfusion (3)(3)

Hemolytic Crisis (Acute Hemolytic Crisis (Acute Transfusion Reaction)Transfusion Reaction)Most commonly caused by ABO incompatibility

May result in activation of coagulation cascade (DIC)

Symptoms and signs◦Headache, back pain, joint pain, anxiety, fever, tachycardia, hypotension, wheezing, pulmonary edema, and renal failure

◦Delayed reactions occur in extravascular space, most commonly spleen, liver, or bone marrow

◦Pink serum or urine

ManagementStop transfusionIV fluids◦Maintain urine output at 30 to 100 cc/h

Hemolytic Crisis (Acute Hemolytic Crisis (Acute Transfusion Reaction) Transfusion Reaction) (2)(2)

Other ComplicationsOther Complications

Febrile transfusion reactionEtiology: recipient antibody response to donor leukocytes, and release of cytokines that are produced in storage

Difficult to differentiate from hemolytic reaction

Management: stop transfusion until hemolytic reaction excluded

SPECIFIC DRUG SPECIFIC DRUG THERAPIES AFFECTING THERAPIES AFFECTING HEMOSTASISHEMOSTASIS

AspirinAspirin

MechanismIrreversibly blocks conversion of arachidonic acid into thromboxane A2 (platelet aggregation agent) by inhibiting cyclooxygenase (COX)

Effect on platelets irreversible, lasts for entire platelet life span (~7 to 10 days)

MechanismIrreversibly blocks ADP receptor on platelets

Deforms the fibrinogen receptor on platelet, that renders the platelet unable to aggregate via the GP IIb and GP IIIa pathway

Clopidogrel and Clopidogrel and TiclopidineTiclopidine

Clopidogrel and Clopidogrel and Ticlopidine (2)Ticlopidine (2)ComplicationsDyspepsia, rash, diarrheaTiclopidine is associated with hematologic effects◦Neutropenia◦ITP◦TTP

ReversalPlatelet transfusion

HeparinHeparinMechanismReduced thrombin and fibrin formation by binding and activating antithrombin III (potentiate activities of antithrombin III)

Unfractionated Heparin Derived from bovine lung tissue Inhibits factors Xa and IIa in roughly equal proportions

Requires frequent monitoring of aPTT (target generally between 1.5 and 2.5 times baseline)

HeparinHeparin

Low Molecular Weight Heparin

Derived from porcine intestinal mucosa

Higher ratio of antifactor Xa to antifactor Iia activity than unfractionated heparin

Activity onset within 3 to 5 hours

ComplicationsHIT

ReversalReversed with protamine sulfate (derived from fish sperm; beware hypotension and anaphylaxis)

HeparinHeparin

Heparin Induced Heparin Induced ThrombocytoeniaThrombocytoeniaHIT is a syndrome of antibody-mediated thrombocytopenia that paradoxically is often associated with thrombosis [thrombotic risk is more than 30 times that in control populations]

Platelet factor 4, a small peptide stored within the alpha granules of platelets, binds to heparin and is released into the blood during treatment with heparin.

These complexes then activate platelets [contributes to the thrombotic complications of heparin-induced thrombocytopenia]

Heparin Induced Heparin Induced ThrombocytoeniaThrombocytoenia

Typically, HIT begins with the appearance of thrombocytopenia about a week after the start of heparin therapy.

Patients who have HIT should not be treated with low-molecular-weight heparins, since these have high cross-reactivity with circulating PF4–heparin antibodies.

Heparin Induced Heparin Induced ThrombocytoeniaThrombocytoenia

HIT Type 1 and 2HIT Type 1 and 2

WarfarinWarfarinMechanismInhibits synthesis of vitamin K-dependent coagulation factors (factors II, VII, IX, and X)

Also inhibits the anticoagulants protein C and protein S

Ingredient in many rodenticides or “superwarfarins”

Warfarin (2)Warfarin (2)

ReversalReversed with FFP or prothrombin complex concentrate

May be reversed with vitamin K◦Oral route preferred, unless rapid reversal required (may administer intravenously)

◦Delay (up to 24 hours) in onset

GP IIb and GP IIIa GP IIb and GP IIIa Receptor InhibitorsReceptor InhibitorsExamples: abciximab, eptifibatide, tirofiban

Mechanism Inhibit platelet aggregation and activation by preventing activated fibrinogen binding to GP IIb/IIIa receptors

Effects typically last 24 to 48 hours

Complications Thrombocytopenia, Hemorrhage

Reversal Platelet transfusion, Desmopressin (may be beneficial)

ONCOLOGIC ONCOLOGIC EMERGENCIESEMERGENCIES

Neutropenic FeverNeutropenic FeverDefinitionSingle oral temperature of ≥38.3°C (101°F)

or sustained temperature elevation of 38°C (100.4°F) for 1 hour and

Polymorphonuclear leukocyte count <500 to 1000 cells/mm3

DiagnosisAll neutropenic patients with fever should be managed as if they have a serious bacterial infection

Cultures (blood, urine, and other areas as indicated)

Radiographic imaging as indicated (eg, chest radiographs, CT sinuses, etc.)

Neutropenic Fever (2)Neutropenic Fever (2)

ManagementAdmission, Start prophylactic empiric antibiotic therapy◦Monotherapy

Imipenem and cilastatin Ceftazidime Cefipime

◦Combination therapy Ceftazidime or cefepime or imipenem/ cilastatin and vancomycin For suspected MRSA (recent hospitalizations) or with indwelling catheter

Neutropenic Fever (3)Neutropenic Fever (3)

ComplicationsUntreated neutropenic fever associated with 20% mortality rate compared to <2% if treated promptly◦Infections are the number one cause of cancer death

◦Remember: Although fever may result from the malignancy itself, 55% to 70% of fevers in this patient population will have an infectious etiology

Neutropenic FeverNeutropenic Fever

Tumor Lysis SyndromeTumor Lysis SyndromeDefinition◦Electrolyte abnormalities that result from the breakdown products of dying cancer cells

Etiology◦Typically following chemotherapy of Leukemias and lymphomas (especially Burkitt lymphoma)

◦Small cell lung carcinoma◦Following steroid administrations

Symptoms and signsOccurs most commonly within 1 to 5 days of initiating chemotherapy or radiation therapy for rapidly growing tumors

Reflect the presenting electrolyte abnormality

Tumor Lysis Syndrome Tumor Lysis Syndrome (2)(2)

Diagnosis (constellation of the following metabolic disturbances)

Hyperuricemia (>7 or 8 mg/dL)◦Secondary to DNA degradation◦Acute renal failure

Hyperkalemia◦Susceptible to arrhythmias◦Exacerbated by renal failure

Tumor Lysis SyndromeTumor Lysis Syndrome

Diagnosis (constellation of the following metabolic disturbances)

Hyperphosphatemia◦Secondary to protein degradation◦Precipitation with calcium in heart and kidney

Hypocalcemia◦Secondary to hyperphosphatemia◦Muscle weakness and cramps

Tumor Lysis SyndromeTumor Lysis Syndrome

a review on hematology and oncology emergencies

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