hematology for surgeons
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Hematology for Surgeons. Michael H. Rosove, MD Clinical Professor of Medicine UCLA Division of Hematology-Oncology November 13, 2013. Anemias. Abrupt post-op drop in Hgb ― post-op equilibration, acute bleeding, or hemolysis Sickle cell disorders Thrombotic microangiopathies - PowerPoint PPT PresentationTRANSCRIPT
Hematology for Surgeons
Michael H. Rosove, MDClinical Professor of Medicine
UCLA Division of Hematology-Oncology
November 13, 2013
Anemias
Abrupt post-op drop in Hgb ― post-op equilibration, acute bleeding, or hemolysis
Sickle cell disorders
Thrombotic microangiopathies
Autoimmune and alloimmune hemolysis
Miscellaneous hemolytic anemias ― sepsis (especially Clostridium perfringens), liver disease, shear-related
Anemias
Sickle (Hgb S) disorders
Hgb SS > SC and S-β thalassemia > AS
Severity lessened by α-thalassemia minor, elevated Hgb F (hereditary persistence or hydroxyurea)
Problems: small vessel thrombotic occlusion (bone pain crisis, in situ pulmonary infarction, ischemic stroke, splenic or renal infarction), ↑ VTE risk
Management: avoid dehydration and hypoxemia, pre-op transfusion (to raise % Hgb A) in severe cases, VTE prophylaxis in appropriate settings
AnemiasThrombotic microangiopathies (TMAs)
Precapillary microvascular thrombosis, red cell fragmentation, thrombocytopenia, end-organ dysfunction/damage
TMA may follow organ transplantation ― especially kidney, lung, and allogeneic marrow stem cell transplantation
Target organ: Predominantly kidneys
Predisposing factors: Allograft rejection, infections, combined calcineurin and mTOR inhibitor therapies
Plasma exchange not known to be effective
? role for eculizumab (C5 inhibitor)
AnemiasAutoimmune hemolysisCauses: drugs, infectionsSpherocytosis (+ agglutination), DAT+, IgG + C3,
antibody screen or RBC eluate shows non-specific warm auto
Treatment: Dependent on cause and severityAlloimmune hemolysisCauses: “Major hemolytic” transfusion reaction
“Delayed hemolytic” transfusion reactionIV IgLiver transplant ― recipient has an RBC antigen the
allograft lacksSpherocytosis (+ agglutination), DAT+, antibody screen
or RBC eluate shows antigen specificityTreatment: Dependent on cause and severity
Anemias
Jehovah’s Witness
Determine which blood component(s) the patient will accept, including CellSaver blood
Be sure the patient understands the risks of refusing blood products
Ask the hardest question and document ― “If your life depended on a blood transfusion, would you prefer to die or to receive transfusion?”
Have the patient and spouse or next of kin (who may have minor dependents) release the physicians and hospital from responsibility for an adverse outcome due to refusal of blood products
Treatment options: Iron, erythropoietin, oxygen, non-blood product treatment of coagulopathy
Coagulopathies
Tests: Protime (INR), PTT, fibrinogen, D-dimers, occasionally factor level(s), ? bleeding time
Only a few causes of isolated prolonged PT:
Mild vitamin K deficiency or warfarin effect
Mild liver dysfunction
Mild DIC
Congenital factor VII deficiency (any severity)
Mild common coagulation pathway deficiencies (congenital deficiency of factor X, V, II, or fibrinogen)
Coagulopathies
Only a few causes of isolated prolonged PTT:
Mild liver dysfunction
UFH, LMWH, fondaparinux, bivalirudin
Congenital deficiency of VIII (including VWF), IX, XI, XII, prekallikrein, HMW kininogen)
Lupus anticoagulant (common)
Acquired factor VIII inhibitor (rare)
Coagulopathies
Clinical consequences depend on cause of prolonged PTT!
Cause PTT Consequence
Factor VIII inhibitor 50 sec Major spontaneousbleeding
Severe XII deficiency 120 sec Not a bleeding disorder
(factor XII 1%)
Mild von Willebrand disease 35 sec Surgical bleeding
(factor VIII and VWF 40%)
Lupus anticoagulant 45 sec Thrombotic tendency
Coagulopathies
Only a few causes of combined prolonged PT/PTT:
Dilutional coagulopathy (during exsanguination or plasmapheresis)
DIC / fibrinolysis
Severe liver dysfunction
Anticoagulants
Congenital deficiency (factor X, V, V/VIII, II, fibrinogen)
Acquired factor V inhibitor (topical bovine thrombin)
Acquired factor X deficiency (primary amyloidosis)
Coagulopathies
Only a few causes of hypofibrinogenemia:
Dilutional coagulopathy (exsanguination, plasmapheresis)
DIC / fibrinolysis
Severe liver dysfunction
Congenital
Coagulopathies
Bleeding disorders with normal PT, PTT, fibrinogen:
Thrombocytopenia and platelet dysfunction
von Willebrand disease (common)
mild hemophilia (VIII or IX) carrier state in women
factor XIII deficiency (very rare)
Available treatments for bleeding disordersFFP ― all clotting factorsCryoprecipitate ― fibrinogen, VWF, VIIIConcentrates ― VIII, VWF, IX (including “4-factor
concentrates”), XIIIRecombinant VIIa ― for factor VIII or IX inhibitors,
congenital factor VII deficiencyFEIBA (factor VIII inhibitor bypassing activity)Vitamin K ― to prevent/correct deficiency, reverse warfarinDDAVP (desmopressin) ― raises factor VIII/VWF levelsAminocaproic and tranexamic acid ― mild fibrinolytic
inhibitionHigh-dose conjugated estrogens ― multiple effectsProtamine sulfate ― reverses UFH well and LMWH
somewhatTPO receptor agonists ― may raise platelet count
Initial approach to the exsanguinating patient
Identify the site of bleeding, and target it for attention
Establish enough large-gauge venous accesses
Aggressive volume resuscitation to avoid shock state
Avoid pressors if possible
RBC transfusion
Blood products to avoid dilutional coagulopathy
FFP
cryoprecipitate
platelet transfusion
If bleeding is diffuse oozing and refractory, then consider some combination of a fibrinolytic inhibitor and high-dose conjugated estrogens
Indications/risks of transfusing blood productsRBC indications: “severe” or symptomatic anemia,
especially with ongoing bleeding or hemolysis
Platelet (single- or multiple-donor) indications:
<100,000 with serious active bleeding
<75,000 with upcoming invasive intervention
<20,000 with sepsis or other bleeding liabilities
<10,000
Volume overload
Alloimmunization; cross-matching difficulties and resulting delays
Hepatitis C and HIV, other infections
Allergic reactions
Thrombophilia testing
dRVVT ― anticoagulants may produce “borderline” results
Cardiolipin and beta2-glycoprotein I antibodies ― always valid
ATIII ― GAG anticoagulants and DIC consume it
PS ― half bound to C4bBP, an acute phase reactant; order total Ag, not activity
PS, PC, ATIII ― all reduced if liver dysfunction present
VIII ― an acute phase reactant
Factor V Leiden and prothrombin G20210A ― invalid in OLT and BMT pts; APCR (activated protein C resistance ratio) is valid, factor II (prothrombin) is valid if protime is normal
The anticoagulants
Glycosaminoglycans (GAGs) ― UFH, LMWH (e.g., enoxaparin), fondaparinux
Vitamin K antagonist ― warfarin
Parenteral anti-thrombins ― argatroban (Argatroban), bivalirudin (Angiomax)
Oral anti-thrombin ― dabigatran (Pradaxa)
Oral anti-Xa’s ― rivaroxaban (Xarelto), apixaban (Eliquis)
Glycosaminoglycan Anticoagulants
heparin (UFH) LMWH Fondaparinux
Source Porcine/bovine Altered UFH Synthetic
Mean # saccharides 36 13 5
Action ATIII, IIa>Xa ATIII, Xa>IIa ATIII, Xa
Plasma protein binding +++ + +
Bioavailability Variable 90% 100%
Half-life, hr Variable, ~6 (SQ) ~6 (SQ) ~17 (SQ)
<1-3 (IV)
PF4 binding ++ ++ ++
GAG/PF4 antibodies ++ ++ ++
HIT 1%-3% 0.3%-0.8% Almost never
Effect of renal dysfunction ++ ++ ++
Monitoring PTT Anti-Xa Anti-Xa
Protamine as antidote ++ + –
Pregnancy category C B B
Heparin-induced thrombocytopenia
HIT remains primarily a clinical diagnosis!Platelet count falls between d. 4-14 of de novo therapy
by 50% of greaterConsider other causes of thrombocytopeniaHeparin-PF4 EIA usually strongly positive, almost never
negative, IgG-only assays improve specificity; SRA more specific but time-consuming, expensive
Thrombosis (anywhere) occurs in about 30% of cases, may be multifocal, often devastating, often litigates
Platelet count usually recovers quicklyPatients remain hypercoagulable for about 2 wksArgatroban dosage is reduced for hepatic insufficiencyBivalirudin dosage is reduced for renal insufficiency
The newer anticoagulants
Acute AF Ortho VTE
HIT VTE proph proph proph ACS
Argatroban *
Bivalirudin * *
Dabigatran * * *
Rivaroxaban * * * *
Apixaban * * *
* = FDA approved indication
* = non-FDA approved indication
GAGs and VKAs — Still Important
Cardiopulmonary bypass: UFHProsthetic heart valves: VKAChronic valvular AF: VKAChronic non-valvular AF: VKA still acceptable if TTR very
good and/or patient can’t afford a new anticoagulantHypercoagulability of malignancy: GAGsAntiphospholipid syndrome: VKANon-orthopedic med/surg VTE prophylaxis: GAGs or VKAPregnancy: GAGsBreast feeding: GAGs or VKAAdvanced renal failure: UFH, VKAMorbid obesity: GAGs, VKA