haematology in 1 hour
DESCRIPTION
Haematology in 1 hour. Approach to low blood count. Consider cause Is it a lack of production = bone marrow problem (intrinsic or extrinsic) Is it excess destruction = immune or other causes Is it excess consumption = sepsis, haemorrhage, large spleen etc Always consider Drugs - PowerPoint PPT PresentationTRANSCRIPT
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Haematology in 1 hourHaematology in 1 hour
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Approach to low blood countApproach to low blood count
Consider causeConsider cause– Is it a lack of production = bone marrow Is it a lack of production = bone marrow
problem (intrinsic or extrinsic)problem (intrinsic or extrinsic)– Is it excess destruction = immune or other Is it excess destruction = immune or other
causescauses– Is it excess consumption = sepsis, Is it excess consumption = sepsis,
haemorrhage, large spleen etchaemorrhage, large spleen etc
Always consider DrugsAlways consider Drugs
Consider Consider inheritedinherited vsvs acquiredacquired
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Approach to the investigation of Approach to the investigation of AnaemiaAnaemia
MCV
LOW NORMAL HIGH
Film appearance
History-diet
-drugs-alcohol
Normal
Assess iron statusFerritin
Iron deficiencyNormal
(or raised)? Ethnic origin
Define and treat cause
Treat with Fe
Establish response
Hb screen
thal trait(Putative thal trait)
Counsel
Associated FBC abnormalities
Liver function inc GT
B12/folateThyroid function
Treat appropriately
SpherocytesAbnormal cell
shapes
Raised ESR
Investigate for ACD
DATReticulocyte count
Refer to Haematologist for further investigation
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Microcytic anaemia -questionsMicrocytic anaemia -questions
Is it iron deficiency or thalassaemia?Is it iron deficiency or thalassaemia?– or both?or both?
If iron deficiency: If iron deficiency: – what is the cause?what is the cause?– what further investigations are required?what further investigations are required?– What is the treatment?What is the treatment?– What if the patient fails to respond to oral What if the patient fails to respond to oral
iron?iron?
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Iron deficiencyIron deficiency
Produces a drop in MCV proportional to the degree of Produces a drop in MCV proportional to the degree of anaemiaanaemiaRDW increases, reflecting anisocytosisRDW increases, reflecting anisocytosisBeware effect of acute disease in interpretation of Beware effect of acute disease in interpretation of Ferritin and TIBC resultsFerritin and TIBC resultsBeware of counteracting effect of drugs/alcohol causing Beware of counteracting effect of drugs/alcohol causing macrocytosis on MCV in iron deficiency – look at macrocytosis on MCV in iron deficiency – look at previous resultsprevious resultsTreatment dose is 200 mg Fe/day (=200mg tds of Treatment dose is 200 mg Fe/day (=200mg tds of Feso4, look up other Fe preparations in BNFFeso4, look up other Fe preparations in BNF
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Failure to respond to oral ironFailure to respond to oral iron
Insufficient dose Insufficient dose
Thalassaemia traitsThalassaemia traits
Non complianceNon compliance
Continuing lossesContinuing losses
Malabsorption (coeliac disease, post Malabsorption (coeliac disease, post gastrectomy)gastrectomy)
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Thalassaemia traitsThalassaemia traits
Produce microcytic, hypochromic indices Produce microcytic, hypochromic indices Clinically asymptomaticClinically asymptomaticMild anaemia, MCH<27pgMild anaemia, MCH<27pgLook for steady state Hb in notes – will tell if additional Look for steady state Hb in notes – will tell if additional problemproblemDo not give iron unless iron deficiency provenDo not give iron unless iron deficiency proven thalassaemia trait causes raised Hb A2thalassaemia trait causes raised Hb A2 thal traits by exclusion of other causesthal traits by exclusion of other causesIn antenatal context identification of b thal trait in women In antenatal context identification of b thal trait in women mandates partner screeningmandates partner screening
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Haemolytic anaemia questionsHaemolytic anaemia questions
How is diagnosis of haemolytic anemia How is diagnosis of haemolytic anemia made?made?– Clinical – jaundice, dark urine, splenomegalyClinical – jaundice, dark urine, splenomegaly– Lab-normocytic anemia, unconjugated Lab-normocytic anemia, unconjugated
hyperbilirubinaemia, reticulocytosishyperbilirubinaemia, reticulocytosis– Further tests: direct antiglobulin test Further tests: direct antiglobulin test
(Coombs), blood film, Hb screen(Coombs), blood film, Hb screen
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Haemolytic anaemiaHaemolytic anaemia
Consider causeConsider cause– Inherited: haemoglobinopathy, membrane Inherited: haemoglobinopathy, membrane
disorderdisorder– Acquired: drugs, transfusion reaction, immune Acquired: drugs, transfusion reaction, immune
disordersdisorders
Treatment directed at causeTreatment directed at cause
Transfuse if symptomatic (problems with Transfuse if symptomatic (problems with cross match)cross match)
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Sickle cell disease: clinical Sickle cell disease: clinical problemsproblems
AnaemiaAnaemia
InfectionsInfections
Painful crisesPainful crises
StrokeStroke
Leg ulcersLeg ulcers
Visual lossVisual loss
Chronic organ damageChronic organ damage– Kidneys, lungs, joints, heartKidneys, lungs, joints, heart
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Sickle cell basic factsSickle cell basic facts
Not exclusive to black racesNot exclusive to black racesHb SS steady state Hb 7-9g/dlHb SS steady state Hb 7-9g/dlTransfuse only for certain indicationsTransfuse only for certain indicationsMilder forms may have normal Hb so Milder forms may have normal Hb so always do Hb Screen if suspicion or pre opalways do Hb Screen if suspicion or pre op% Hb S is constant and bears no relation % Hb S is constant and bears no relation to acute crisisto acute crisisPatients have functional asplenia, Patients have functional asplenia, therefore high risk of infectiontherefore high risk of infection
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Macrocytic anaemia - questionsMacrocytic anaemia - questions
Is it a new problem?Is it a new problem?
Is it due to alcohol?Is it due to alcohol?
Is it due to diet /haematinic deficiencyIs it due to diet /haematinic deficiency
Is it due to drugs?Is it due to drugs?
When to refer to the haematologist?When to refer to the haematologist?
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Management of low B12Management of low B12
HistoryHistory– Diet, previous surgery, GI diseaseDiet, previous surgery, GI disease
IF antibodiesIF antibodies– Schilling test no longer availableSchilling test no longer available
Symptoms/signs - give i.m. B12 with folic acidSymptoms/signs - give i.m. B12 with folic acid– levels unhelpful and unnecessary after thislevels unhelpful and unnecessary after this
Asymptomatic - ?dietary can give oral B12 and reassess Asymptomatic - ?dietary can give oral B12 and reassess levels after a few weekslevels after a few weeksFailure to respond to haematinics may indicate MDSFailure to respond to haematinics may indicate MDS
n.b. if normal Hb, MCV can take several weeks to falln.b. if normal Hb, MCV can take several weeks to fall
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PolycythaemiaPolycythaemia
Raised haematocrit (in well hydrated Raised haematocrit (in well hydrated patient)patient)Consider causeConsider cause
– primary (uncommon) v secondary primary (uncommon) v secondary (common)(common)
– cause of secondarycause of secondaryHypoxia (respiratory disease, smoking, cardiac Hypoxia (respiratory disease, smoking, cardiac disease R – L shunt)disease R – L shunt)Excessive EPO (renal /hepatic disease/tumours)Excessive EPO (renal /hepatic disease/tumours)
Increased thrombotic riskIncreased thrombotic risk
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PolycythaemiaPolycythaemia
Investigations, if not apparent from historyInvestigations, if not apparent from history– CXR, Arterial gas, lung function, EPO levelCXR, Arterial gas, lung function, EPO level
Refer to haematology if no obvious Refer to haematology if no obvious secondary causesecondary cause
Management: Venesection to Hct as Management: Venesection to Hct as defined for underlying causedefined for underlying cause
Chemotherapy (primary cause)Chemotherapy (primary cause)
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Raised WBC questionsRaised WBC questions
Is it confined to one type of cell or all white Is it confined to one type of cell or all white cells?cells?
Are abnormal cells present?Are abnormal cells present?
What are appearances of blood film?What are appearances of blood film?
Common cause is reactive (neutrophilia, L Common cause is reactive (neutrophilia, L shift, in context of shift, in context of infection/inflammation/malignancy)infection/inflammation/malignancy)
CRP may be a pointer to reactive causeCRP may be a pointer to reactive cause
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LeukaemiaLeukaemia
Clonal proliferations of one of more types Clonal proliferations of one of more types of white cellsof white cellsMature cells = chronic leukaemiaMature cells = chronic leukaemia– CLLCLL lymphocyteslymphocytes– CMLCML Mature + immature Myeloid cellsMature + immature Myeloid cells
Immature cells = acute leukaemiaImmature cells = acute leukaemia– characterised by presence of blasts and characterised by presence of blasts and
immature cells in blood/BMimmature cells in blood/BM– e.g AML, ALLe.g AML, ALL
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Effects of leukaemiaEffects of leukaemia
Bone marrow failureBone marrow failure– anaemiaanaemia– thrombocytopenia - bleeding riskthrombocytopenia - bleeding risk– neutropenia - infection riskneutropenia - infection risk
Tissue infiltrationTissue infiltration– Tumour deposits e.g skin, nodes, gums,CNS, Tumour deposits e.g skin, nodes, gums,CNS,
liver or spleenliver or spleen
Immune suppression - infectionImmune suppression - infectionDeath usually due to infection or bleedingDeath usually due to infection or bleeding
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How does acute leukaemia How does acute leukaemia present?present?
InfectionInfectionSymptoms of anaemiaSymptoms of anaemiaBruising/bleedingBruising/bleedingTissue infiltrationTissue infiltrationBlood film shows cytopenias with blastsBlood film shows cytopenias with blastsConfirm on Bone marrow and Confirm on Bone marrow and immunophenotyping/cytochemistry. Chromosomesimmunophenotyping/cytochemistry. ChromosomesTreatment: intensive chemotherapyTreatment: intensive chemotherapyPrognosis: depends on characterisitcs and patient Prognosis: depends on characterisitcs and patient comorbidity. e.g childhood ALL very good prognosis, comorbidity. e.g childhood ALL very good prognosis, elderly AML, poorelderly AML, poor
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Chronic leukaemiaChronic leukaemia
May be incidental finding e.g CLLMay be incidental finding e.g CLLAssociated with symptoms/signs of marrow Associated with symptoms/signs of marrow infiltrationinfiltrationIncreased infections (bacterial/fungal)Increased infections (bacterial/fungal)LymphadenopathyLymphadenopathyAutoimmune features eg AIHA in CLLAutoimmune features eg AIHA in CLLDiagnosis on film/marrow/special investigationsDiagnosis on film/marrow/special investigationsTreatment variable: observation only to intensive Treatment variable: observation only to intensive chemotherapychemotherapyPrognosis very variable eg. CLLPrognosis very variable eg. CLL
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What are lymphomasWhat are lymphomas
neoplasms of lymphoid origin, neoplasms of lymphoid origin, typically causing lymphadenopathytypically causing lymphadenopathy
leukaemia vs lymphomaleukaemia vs lymphoma
lymphomas are clonal expansions of lymphomas are clonal expansions of cells at certain developmental stagescells at certain developmental stages
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A practical approach to lymphomasA practical approach to lymphomas
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable – months to years
Curable in most
Treat
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Clinical manifestationsClinical manifestationsVariableVariable
severity: asymptomatic to extremely illseverity: asymptomatic to extremely ill
time course: evolution over weeks, months, or time course: evolution over weeks, months, or yearsyears
Systemic manifestationsSystemic manifestationsfever, night sweats, weight loss, anorexia, fever, night sweats, weight loss, anorexia, pruritispruritis
Local manifestationsLocal manifestationslymphadenopathy, splenomegaly most lymphadenopathy, splenomegaly most commoncommon
any tissue potentially can be infiltratedany tissue potentially can be infiltrated
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Other complications of lymphomaOther complications of lymphoma
bone marrow failure (infiltration)bone marrow failure (infiltration)
CNS infiltrationCNS infiltration
immune hemolysis or immune hemolysis or thrombocytopeniathrombocytopenia
compression of structures (eg spinal compression of structures (eg spinal cord, ureters) by bulky diseasecord, ureters) by bulky disease
pleural/pericardial effusions, ascitespleural/pericardial effusions, ascites
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Stage I Stage II Stage III Stage IV
Staging of lymphomaStaging of lymphoma
A: absence of B symptomsB: fever, night sweats, weight loss
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Investigation of suspected Investigation of suspected lymphomalymphoma
Biopsy of affected node/massBiopsy of affected node/mass– ESSENTIAL as dictates treatment and ESSENTIAL as dictates treatment and
prognosisprognosis
Staging CT scans/Bone marrowStaging CT scans/Bone marrow
FBC, Biochemistry, LDH, etcFBC, Biochemistry, LDH, etc
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Three types of lymphoma you will Three types of lymphoma you will most commonly meetmost commonly meet
Follicular lymphomaFollicular lymphoma
Diffuse large B-cell lymphomaDiffuse large B-cell lymphoma
Hodgkins lymphomaHodgkins lymphoma
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Neutropenia questionsNeutropenia questions
Is it isolated or associated with other Is it isolated or associated with other cytopenias?cytopenias?Is it recent or longstanding?Is it recent or longstanding?Is it associated with history of infection?Is it associated with history of infection?Common causes of isolated neutropenia:Common causes of isolated neutropenia:– Viral infection (acute and chronic eg HIV)Viral infection (acute and chronic eg HIV)– Drug related (look up list)Drug related (look up list)– Ethnic (longstanding, asymptomatic, no other Ethnic (longstanding, asymptomatic, no other
cause)cause)
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Severe neutropeniaSevere neutropenia
Infection risk increased if neuts<1.0 x 109/lInfection risk increased if neuts<1.0 x 109/l
High risk of infection of neuts<0.5High risk of infection of neuts<0.5
Risk is also related to duration of neutropenia Risk is also related to duration of neutropenia and neutrophil functionand neutrophil function
Consider prophylaxis of infection if neuts<0.5Consider prophylaxis of infection if neuts<0.5
Fever in Neutropenic patient is a medical Fever in Neutropenic patient is a medical emergency – investigate and treat empirically emergency – investigate and treat empirically with broad spectrum antibiotics pending micro with broad spectrum antibiotics pending micro results. Hospital should have a protocol.results. Hospital should have a protocol.
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ParaproteinsParaproteins
Common incidental finding, esp in elderlyCommon incidental finding, esp in elderly
Due to clonal proliferation of plasma cellsDue to clonal proliferation of plasma cells
Is it significant? Is it significant?
Causes: Causes: – secondary: (autoimmune disorders/infections)secondary: (autoimmune disorders/infections)– Malignant: myeloma/lymphomaMalignant: myeloma/lymphoma– Uncertain: MGUS (20% evolve into clonal Uncertain: MGUS (20% evolve into clonal
disorder)disorder)
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MyelomaMyeloma
Clinical features due to combinations of:Clinical features due to combinations of:– Marrow failureMarrow failure– immunsuppressionimmunsuppression– Paraprotein (renal disease)Paraprotein (renal disease)– Bone disease (pain, fractures, lytic lesions/hypercalcaemia)Bone disease (pain, fractures, lytic lesions/hypercalcaemia)
Investigation of PPInvestigation of PP– HistoryHistory– FBC, Biochem, Serum electrophoresisFBC, Biochem, Serum electrophoresis– Bone X raysBone X rays– Bone marrowBone marrow– MGUS is defined by lack of evidence for malagnancy or reactive MGUS is defined by lack of evidence for malagnancy or reactive
cause.cause.
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Haemostasis and Haemostasis and thrombosisthrombosis
Physiology of haemostasisPhysiology of haemostasisBleeding disorders (congenital)Bleeding disorders (congenital)Massive blood lossMassive blood lossDICDICAnticoagulant drugsAnticoagulant drugs
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Haemostasis needs…Haemostasis needs…
PlateletsPlatelets
Vessel WallVessel Wall
Clotting FactorsClotting Factors
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The starter motor……..
Switched off
by Tissue Factor
Pathway
Inhibitor
Provides initial Thrombin burst
Factors measured in Prothrombin Time
PT
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The engine…………..
Thrombin from initial burst back activates “intrinsic system”
Fibrin then cross linked by XIII
APTT
TT
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Natural anticoagulantsNatural anticoagulants
Protein C (activated by thrombin/thrombomodulin)Protein C (activated by thrombin/thrombomodulin)Protein S - cofactor for protein CProtein S - cofactor for protein C
Protein C and S cleave factors V and VIIIProtein C and S cleave factors V and VIII
Antithrombin inhibits Thrombin and XaAntithrombin inhibits Thrombin and Xa– TAT complexes removed by liver TAT complexes removed by liver – Activity increased 000’s by heparinActivity increased 000’s by heparin
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Global coagulation testsGlobal coagulation tests
•APTT : Kallikrein, HMWK, XII, XI, IX, VIII, X, V, II, I•“intrinsic system”
•PT : VII, X, V, II, I•“extrinsic system”
•TT : I
•50:50 mix with normal plasma will distunguish a lack of clotting proteins from an inhibitor of function
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CAUSES OF A PROLONGED PROTHROMBIN TIME
CONGENITAL •Coagulation factor deficiencies: VII, X, V, II, I
ACQUIRED•Hepatocellular disease•Vitamin K deficiency (II, VII, IX, X): obstructive jaundice, haemorrhagic disease of the newborn•Disseminated intravascular coagulation (DIC)•Massive blood transfusion•Warfarin (monitoring test based on PT)•Gross overheparinisation, some lupus anticoagulants
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CAUSES OF A PROLONGED ACTIVATED PARTIAL THROMBOPLASTIN TIME
CONGENITAL•Coagulation factor deficiencies: XII, XI, IX, VIII, X, V, II, I
ACQUIRED•Hepatocellular disease•Vitamin K deficiency•Disseminated intravascular coagulation•Massive blood transfusion•Heparin (monitoring test based on APTT)•Lupus anticoagulants
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CAUSES OF A PROLONGED THROMBIN TIME
CONGENITAL•Dys/hypofibrinogenaemia
ACQUIRED•Hepatocellular disease: dys/hypofibrinogenaemia•Disseminated intravascular coagulation:
hypofibrinogenaemiaFDPs
•Heparin
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HaemophiliaHaemophilia
A = reduced VIII; B = reduced IXA = reduced VIII; B = reduced IXBoth sex-linked recessiveBoth sex-linked recessiveQueen VictoriaQueen VictoriaIntronic rearrangements, point mutations, gene deletionsIntronic rearrangements, point mutations, gene deletionsHaemophilia A 1 in 10,000 male infantsHaemophilia A 1 in 10,000 male infantsProlonged APTT (normal PT and TT)Prolonged APTT (normal PT and TT)Mild Rx: Tranexamic acid, DDAVP (not HB)Mild Rx: Tranexamic acid, DDAVP (not HB)Severe Rx: factor replacement recombinant or pooled donorSevere Rx: factor replacement recombinant or pooled donor Home prophylaxisHome prophylaxisPast problem with HIV, now HCV ??? CJDPast problem with HIV, now HCV ??? CJD
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Von Willebrand’s DiseaseVon Willebrand’s Disease
Functions of VWF:Functions of VWF:
11. . Sticks to platelets (GPIb)Sticks to platelets (GPIb)
2. Sticks to collagen in subendothelium2. Sticks to collagen in subendothelium
(Important in small blood vessel lesions; high shear stress)(Important in small blood vessel lesions; high shear stress)
3. Binds to and protects VIII (labile)3. Binds to and protects VIII (labile)
Therefore in VWD see long APTT (low VIII) and bleeding where Therefore in VWD see long APTT (low VIII) and bleeding where VWF platelet interaction importantVWF platelet interaction important
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Treatment optionsTreatment optionsDDAVP, antifibrinolyticsDDAVP, antifibrinolyticsNB DDAVP causes fluid retention. NOT for type 2BNB DDAVP causes fluid retention. NOT for type 2BIntermediate purity VIII concentrateIntermediate purity VIII concentrateVWF concentrate (NB takes hours for VIII to follow so may VWF concentrate (NB takes hours for VIII to follow so may need to give both)need to give both)If severe bleeding consider platelet infusion and If severe bleeding consider platelet infusion and cryoprecipitatecryoprecipitate(NB type I may “auto-correct” in pregnancy)(NB type I may “auto-correct” in pregnancy)
Von Willebrand’s DiseaseVon Willebrand’s Disease
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Massive blood lossMassive blood loss
Defined as loss of > one circulating volume in 24 Defined as loss of > one circulating volume in 24 hourshoursCoagulopathy is multifactorial:Coagulopathy is multifactorial:Loss of factors only once 80% of volume replacedLoss of factors only once 80% of volume replacedDilution of factors during fluid resuscitationDilution of factors during fluid resuscitationInhibitory effect of some colloids on clotting factorsInhibitory effect of some colloids on clotting factorsDIC secondary to traumaDIC secondary to traumaAcidosisAcidosisHypothermia (enzymes) (blood warmer)Hypothermia (enzymes) (blood warmer)
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Regular checks of FBC and PT,APTT,TT and FibrinogenRegular checks of FBC and PT,APTT,TT and FibrinogenAim for platelets > 50x10Aim for platelets > 50x1099/l or >100x10/l or >100x1099/l if polytrauma or /l if polytrauma or CNS injuryCNS injuryAim for fibrinogen >1g/lAim for fibrinogen >1g/lAim for PT and APTT <1.5x control timesAim for PT and APTT <1.5x control timesFFP 12-15ml/kgFFP 12-15ml/kgCryoprecipitate 1-1.5 packs /10kg if fibrinogen fails to correct Cryoprecipitate 1-1.5 packs /10kg if fibrinogen fails to correct with FFPwith FFP? rVIIa? rVIIa
Massive blood lossMassive blood loss
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Causes of DICCauses of DIC
sepsis/severe infection (any organism)trauma (e.g. polytrauma, neurotrauma, fat embolism)organ destruction (e.g. severe pancreatitis)malignancymassive blood loss with inadequate fluid replacementvascular abnormalities (e.g. Kassbach-Merrit syndrome)severe hepatic failuresevere toxic or immunological reactions (e.g. recreational drugs, transfusion reactions, transplant rejection)
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Management of DICManagement of DIC
TREAT THE CAUSETREAT THE CAUSE
Fluid resus as needed, antibiotics if sepsisFluid resus as needed, antibiotics if sepsis
If bleeding or need surgery give FFP, Platelets, Cryoprecipitate If bleeding or need surgery give FFP, Platelets, Cryoprecipitate
(Aim Platelets>50x10(Aim Platelets>50x1099/l, PT and APTT < 1.5x normal)/l, PT and APTT < 1.5x normal)
If thrombotic manifestations eg. Dermal ischaemia consider low If thrombotic manifestations eg. Dermal ischaemia consider low dose heparin infusion. dose heparin infusion.
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HeparinHeparin
NB arterial
lines !!!!!!!
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HeparinHeparin
Unfractionated Unfractionated
monitor with APTT (ratio 1.5-2.5 patient’s baseline)monitor with APTT (ratio 1.5-2.5 patient’s baseline)
reversal by stopping infusion and (very rapid with protamine sulphate)reversal by stopping infusion and (very rapid with protamine sulphate)
can be hard to anticoagulate children due to low antithrombin levelscan be hard to anticoagulate children due to low antithrombin levels
bolus then continuous infusionbolus then continuous infusion
Low molecular weight heparinLow molecular weight heparin
less monitoringless monitoring
once or twice daily administrationonce or twice daily administration
more reliable pharmacokinetics (NB renal excretion)more reliable pharmacokinetics (NB renal excretion)
anti-Xa levels - 4h post doseanti-Xa levels - 4h post dose
Treatment 0.5-1; Prophylaxis 0.1-0.3 IU/mlTreatment 0.5-1; Prophylaxis 0.1-0.3 IU/ml
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WarfarinWarfarin
II, VII, IX, X, protein C and S are vitamin K dependent.
NB C and S fall first so overlap with heparin (Warfarin induced skin necrosis)
Therapeutic range within 3-5 days
Monitor in anticoagulant clinic using INR
Most indications target INR 2-3
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Bleeding on warfarinBleeding on warfarin
Treatment based on assessment of bleeding risk and Treatment based on assessment of bleeding risk and INRINR
Usually enough to stop and monitor INR daily until in Usually enough to stop and monitor INR daily until in therapeutic rangetherapeutic range
Reversal with Vitamin K (6-8 hours) – large doses may Reversal with Vitamin K (6-8 hours) – large doses may render subsequent antico difficult)render subsequent antico difficult)
Emergency use Plasma or clotting factor concentratesEmergency use Plasma or clotting factor concentrates
Hospital should have protocolHospital should have protocol