Anemia Bleeding

7/28/2019 Anemia Bleeding

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Anemia and The BleedingPatient

November 1, 2005Eli Denney D.O.


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Definition of Anemia

Anemia a reduced concentration of redblood cells. Measured by Hct, Hgb and RBCcount.

Anything that reduces production or increases destruction will result in anemia if the processes are not corrected.


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Anemia - Causes

Most common causes in U.S.Iron deficiencyThalassemia

Anemia of Chronic Disease


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Physiologic Reactions to Blood Loss

Acute Peripheral vasoconstriction andcentral vasodilatation

If blood loss continues small vessel

dilatation with compensatory decreased PVR,resulting in increased CO.

Chronic - Increased plasma volume keepsintravascular volume normal

Erythropoietin released by kidneys reticulocytes in 3-7 days.


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Signs and Symptoms

Depend uponRate of blood loss

Amount of blood lost

AgeOverall HealthComorbid disease states


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Signs and Symptoms

WeaknessFatigueDyspnea

PalpitationsOrthostaticsymptomsLethargy


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Physical Exam Findings

+ Orthostatic BPs Tachycardia

Pallor Systolic ejc. murmur

Widened pulsepressure

GI bleeding/Uterinebleeding Altered Mental Status


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Diagnosis

Confirmed by lab values RBC count, Hgband Hct.CBC may not determine specific cause

need to obtain other labs to begin appropriateworkup

CBC-provides RBC indices (MCV)Reticulocyte countPeripheral smear Iron studiesFolate, B12 levels


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Treatment

In ED, anemia from hemorrhage is the mostcommon need for treatment

Symptomatic

Hemodynamically unstable Asymptomatic - can do outpatient work up -depends upon clinical situation.

Based on clinical situation, patients should betyped and cross-matched for transfusion

Admit Patients with ongoing blood loss for definitive care


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Increased Likelihood of BleedingDisorder

Spontaneous bleeding-multiple sitesBleeding from untraumatized sites

Bleeding several hours after traumaBleeding into deep tissues or jointsFamily history of bleeding disorder

Excessive bleeding after dental extractions or surgical proceduresLiver disease


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Increased Likelihood of BleedingDisorder

Drugs EthanolCoumadin

ASANSAIDS

AntibioticsPlavix


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Bleeding Site May Indicate SpecificAbnormalities Indicative of PlateletDisorder

Mucocutaneous BleedingPetechiae

EcchymosisEpistaxisGI/GU bleedingHeavy menstrual bleeding

Purpura are associated withthrombocytopenia and commonly indicates asystemic disease


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Coagulation Factor Deficiencies

Bleeding into joints, potential spaces,retroperitoneum and delayed bleeding

Mucocutaneous bleeding and bleeding intodeep spaces may be signs of DIC both

pathways of homeostasis are involved.


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Normal Coagulation

Platelet Plug (Primary Homeostasis)

Cross-linked Fibrin (Secondary Homeostasis)

Fibrinolytic system counter regulatory

system that prevents excessive clotformation.


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Primary Homeostasis

Depends upon platelet interaction withendothelium

Requires normal vascular endothelium,

functional platelets, von Willebrand factor, andnormal fibrinogenvon Willebrand factor connects platelets to theendothelium by glycoprotein Ia

Fibrinogen connects platelets by glycoproteinsIIB-IIIA.


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Secondary Homeostasis

See Fig 218-3 - Coagulation Cascade


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Fibrinolytic System

Purpose is to limit the size of fibrin clotsEndothelial cells release tPA which convertsplasminogen to plasmin which is already a

part of the fibrin clotPlasmin degrades fibrinogen and fibrinmonomer into fibrin degredation products andcross linked fibrin into D-Dimers


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Other Inhibitory Proteins

Antithrombin III inhibits clotting cascade.Inhibits function of XIIa, XIa, IXa andThrombin.

Heparin potentiates this interaction.


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Proteins C and S

Activated Protein C binds with cell surfacebound Protein S the bound proteins inhibitfactors Va and VIIa.


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Inhibitory Proteins

Deficiencies or dysfunction of proteins C,S or antithrombin III can cause a hypercoagulablestate.


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Initial Testing for Bleeding Disorders

CBCPT/INRPTTFurther testing as indicated (Table 218-4)


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Acquired Bleeding Disorders


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Acquired Platelet Defects

Quantitative DefectsDecreased productionIncreased destruction

Splenic sequestrationPlatelet levels less than 10-20,000 / microLincreases the likelihood of spontaneous

bleeding

especially intracranialLevels less than 10,000 transfusion of platelets will be necessary


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Decreased Production

Bone marrow infiltration Aplastic anemiaViral infections CMV, RubellaDrugs (Thiazides, Ethanol, Chemo-agents)Vitamin B12, Folate deficiencyRadiation


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Increased Destruction

ITPTTPHUSDIC

Viral infections HIV, Varicella, EBVDrugs

Heparin/Protamine


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Idiopathic Thrombocytopenic Purpura

Autoimmune disease involvingthrombocytopenia, purpura or petechiae,normal bone marrow function and no other

known cause for decreased platelets. Autoantibodies attach to circulating plateletsand are destroyed by the reticulendothelialsystem.Platelets function normally despite lownumbers and bound with antibodies


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ITP Acute and Chronic Course

Acute typically occurs in children, males =females, duration 1-2 months.Chronic typically occurs in adults, lasts

greater than 3 months, female > male,resolution unlikely even with treatment.Patients with chronic ITP more commonlyhave another disease or autoimmunedisorder.


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ITP PE and Lab

Commonly PE will show petechiae, epistaxis,gingival bleeding, bruising, and possiblemenorrhagia. Remaining PE may be normal.

Lab CBC - low platelets, otherwise normal.Peripheral smear-normal platelets, few innumber If history, PE, and above lab support thediagnosis of ITP, no further ED testing isnecessary.


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Treatment - ITP

Minimize bleeding risks Meds, falls,comorbid disease states and procedures.

Asymptomatic and healthy, with platelet

counts > 50,000 no treatment is needed< 50,000 and symptoms require treatment


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Treatment - ITP

Prednisone 60-100 mg/d tapered after plateletcount returns to normal ranges.If steroid therapy fails splenectomy producesremission in 65 percent of patients.If bleeding is life threatening local hemorrhagecontrol should instituted and high dosemethylprednisolone 1-2 g/d for 2-3 days used.Intravenous immunoglobulin as needed.Platelets transfused after steroids or immunoglobins.


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Drug Induced Thrombocytopenia Table 219-2

Common drugsHeparinSulfas

ASAEthanolThiazides

IndomethacinValproic AcidLasix


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Platelet Sequestration

Splenomegaly and thrombocytopenia withoutsignificant bleeding is not uncommon.

Another bleeding disorder is usually involved

if significant hemorrhage is present.

Splenectomy is the definitive therapy for patients with low counts and evidence of significant hemorrhage.


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Qualitative Platelet Abnormalities

Liver diseaseUremiaDIC

SLEITPCardiopulmonaryBypass

MyeloprolifertivedisordersDysproteinemiasVon WillebrandsdiseaseLeukemias


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Drug Induced Platelet Dysfunction

ASANSAIDSClopidogrelTiclopidine


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Liver Disease

Any disease that affects the hepatocytes canaffect the production of the clotting factorsMalabsorption of Vit. K by primary biliary

cirrhosis and intra and extrahepaticcholestasis will affect factor II, VII, IV, and XIn more severe liver disease, decreasedsynthesis of a2 plasmin inhibitor will cause ageneral state of fibrinolysis and increase D-Dimers and fibrin degradation products


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Lab

To evaluate coagulation in liver disease thefollowing labs will need to be ordered

Hematocrit

PTaPTTPlatelet countFDP and D-Dimer


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Treatment

Lab abnormalities without bleeding patientscan be observedBleeding or invasive procedure needed

treatment is necessaryVitamin K for liver diseaseFFP if prolongation of PT and aPTT

Cryopercipatate if fibrinogen levels < 100mg/dLPlatelet transfusion if indicated -


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Renal Disease

Dialysis related thrombocytopeniaToxin inhibition of platelet aggregation uremic toxins.

For life threatening bleeding, treatment isusually dialysis and transfusion for anemia,DDAVP and conjugated estrogens.Platelet transfusion and cryoprecipitatetransfusions as needed.


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Disseminated Intravascular Coagulation

DIC an acquired syndrome characterizedby activation of the coagulation systemresulting in fibrin formation. The fibrinolytic

system is also activated which breaks downclots, uses all coagulation proteins andresults in bleeding - TintinalliDIC is associated with many conditions Table 219-5


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Pathophysiology

Disease process begins by the activation of tissuefactor extrinsic pathway.Thrombin converts fibrinogen to fibrin leading toformation of small clots that are deposited in

capillaries causing tissue ischemia organdysfunction.Excessive activation of the coagulation system leadsto depletion of coagulation proteins and platelets.tPA is activated indirectly by thrombin and fibrin andthe fibrinolytic system is activated in DIC thesystem works in excess and can result inuncontrolled bleeding


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DIC Manifestations

Hemorrhage and thrombosis both take place,one form usually is dominate.Hemorrhage most dominate

PetechiaeEcchymosesGI/GU bleeding

Wounds/IV sites


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DIC Manifestation

ThrombosisPurpura fulminansMental Status Changes

MOFOliguria

ARDS

Tissue necrosisIn chronic DIC the liver produces enoughcoagulation proteins to compensate


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DIC - Lab

Increased PTThrombocytopenia most commonLow fibrinogen levels

Fibrinogen levels less than 100 mg/dL, - morelikely to see bleeding complications

D-Dimers are more specific than FDPs in

diagnosing DICIncreased LDH, decreased haptoglobin,schistocytes on peripheral smear


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DIC Treatment

Treatment of underlying disease triggering DICHemodynamic support as needed PRBCs, IVFs,vasopressors as needed.Supplementation of coagulation proteins, platelets

and fibrinogenCryoprecipitate in 10-unit doses to keep fibrinogen to100-150 mg/dLPlatelet transfusion if < 20,000 or < 50,000 withbleedingFFP transfused at 10-15 mL/kg to replace clottingproteinsVitamin K, Folate


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DIC Treatment

Heparin for thrombotic dominant DIC or chronic DIC and known clots purpurafulminans

Antifibrinolytic agents are withheld for provenhypofibrinogenemia and fibrinolysis. Heparinshould be infused before to decrease chanceof thrombosis


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HIV Bleeding Disorders

Thrombocytopenia is one of the earliest signsof HIV infectionBleeding problems are uncommon, the mostcommon problems being bruising, mucosalbleeding and petechiaeThrombocytopenia caused by

Increased destruction immune complex

related and HIV medicationsDecreased synthesis immune complexrelated and HIV medications


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HIV Bleeding Disorders

HIV patients commonly haveLupus anticoagulant increased aPTT, whichmay appear and disappear with infection

Anticardiolipin antibody rarely causes adisorder in itself


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Circulating Anticoagulants

Antibodies that affect coagulation factorsKnown inhibitors for each coagulation proteinexist but the two most common are

Factor VII inhibitors Antiphospholipid antibodies lupusanticoagulant and anticardiolipin antibodies.


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Factor VIII Inhibitors

Can develop at any time but usually affectpatients with hemophilia APatients at risk of developing factor VIIIinhibitors

ElderlyPostpartum patients

Autoimmune disorders SLE, RA, UC, Mult.

MyelomaHave drug reactions PCNs, Sulfas,Phenytoin


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Signs and SymptomsLarge bruising without traumaEcchymoses

HematomasLabNormal PTNormal Thrombin clotting time

Prolonged aPTT does not correct after mixingFactor VIII assay will be low


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Treatment of Bleeding EpisodesPressure to bleeding siteFactor VIII concentrates

Factor IX complex concentratesProthrombin complex concentratesRecombinant factor VIIIa concentrates

PlasmaphersisUltimately a hematologist should direct carefor life or limb threatening bleeding episodes


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Antiphospholipid Antibody Syndrome

Presence of lupus anticoagulant or anticardiolipin antibodies, plus one or both of the following: thrombosis and/or

complications with pregnancy (recurring fatalloss


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In reality SLE patients rarely have theantibody (5-15 percent) in vivo patientsdevelop clots rather than bleed.

Lupus anticoagulant more common in HIVpatients, cancer, drug reactions and other autoimmune disorders

Anticardiolipin antibodies commonly occur with lupus anticoagulant but both can occur separately


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Lupus anticoagulant lab abnormalitiesNormal or prolonged PTProlonged aPTT does not correct when mixedNormal Thrombin clotting timePatients may develop antibodies to prothrombincausing a deficiency suggested by markedlyprolonged PTFactor assays all factors will be mildly low

Russell viper venom time detects presence of lupusanticoagulant

Anticardiolipin antibodies detected by ELISA assay


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Signs and SymptomsThromboembolism venous > arterialPregnancy complications

ThrombocytopeniaPatients who develop thrombosis and remainpositive for lupus anticoagulant have a 50percent chance of another clot forming within

2 yearsRecurrent fetal loss most likely due tothrombosis of placental vessels


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Treatment Asymptomatic observation, reduce risks for Virchows triad.

Treat underlying disorder if knownCorticosteroids for both AAS and autoimmunedisease together Patients with episodes of thrombosis needlifelong anticoagulation

ASA alone is inadequateLMWHs good role for these medicines


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Bibliography

Tintinalli Judith E., Emergency Medicine AComprehensive Study Guide 6 th Edition.Chapters 218-219

Q i


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Questions

T/F Lupus Anticoagulant is always present inpatients with SLE?T/F von Willebrand disease is a disorder of the extrinsic clotting pathway?T/F Definitive treatment of DIC is heparinfollowed by coumadin therapy?T/F Defiencies of proteins C and S cause

thrombotic disorders?T/F This was a fun and interesting chapter?F, F, F, T, F

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Anemia Bleeding