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ACQUIRED BLEEDING DISORDERS

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ACQUIRED BLEEDING DISORDERS. Kevin A Rickard. Royal Prince ... Porcine FVIII. FVIIa. FEIBA. Plasmapheresis. CIRCULATING ANTICOAGULANTS. Lumpus like inhibitor ... – PowerPoint PPT presentation

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Title: ACQUIRED BLEEDING DISORDERS


1
ACQUIRED BLEEDING DISORDERS
  • Kevin A Rickard
  • Royal Prince Alfred Hospital

2
ACQUIRED BLEEDING DISORDERS
  • HAEMOSTASIS
  • EVALUATION
  • History and Examination
  • Laboratory Tests
  • FBC Hb WCC Platelets
  • Coagulation Prothrombin time
  • II V VII X
  • APTT
  • VIII IX XI XII
  • Factor assays
  • Prothrombin Time 10 secs N
  • Prothrombin Ratio 20 secs P 20 2
  • 10

3
ACQUIRED BLEEDING DISORDERS
  • HAEMOSTASIS
  • Platelets Coagulation Fibrinolysis
  • HAEMOSTATIC FAILURE
  • Congenital or acquired disorders affecting the
    above
  • Coagulation Defects
  • Platelet abnormalities
  • Fibrinolysis
  • Combination defects

4
ACQUIRED BLEEDING DISORDERS
  • COAGULATION DEFECTS
  • LIVER DISEASE Multiple factors
  • DEFIBRINATION SYNDROME
  • ANTICOAGULANT OVERDOSE
  • Heparin
  • Warfarin
  • VITAMIN K DEFICIENCY
  • CIRCULATING ANTICOAGULANTS
  • FVIII inhibitors
  • Lupus like
  • Antiphospholipid
  • Anticardiolipid

5
ACQUIRED BLEEDING DISORDERS
  • PLATELET DEFECTS
  • Dilutional thromocytopenia
  • Thombopathy
  • Nutritional
  • Infective
  • FIBRINOLYSIS
  • Fibrinolytic agents
  • Secondary fibrinolysis

6
LIVER DISEASE
  • Acute or Chronic
  • Acute Hepatitis Hepatic failure
  • Chronic Chronic Active Hepatitis
  • Cirrosis
  • Mechanisms
  • Coagulation proteins synthesised in the liver
  • Portal circuit hypertension
  • Splenomegaly - hypersplenism
  • Oesvarices - Tpenia
  • Fibrinolytic activation
  • Non clearance of activators
  • Reduced inhibitors ?2 antiplasmin
  • Naturally occurring anticoagulants
  • ATIII, protein C, protein S ?
  • ? Haemostatic balance lower level

7
LIVER DISEASE
  • Hepatic impairment - insufficiency
  • Lab Tests
  • PT ? APTT ? Fibrinogen ?
  • Assays II, V, VII, IX, X, ?
  • VIII ?
  • Tpenia
  • Fibrinolysis ?
  • Clinically
  • Bruising
  • Bleeding
  • General
  • Gastro intestinal
  • Bleeding multifactorial
  • Coag factors ?
  • Tpenia ?
  • Physical site

8
LIVER DISEASE
  • Haemostatic Failure
  • Therapy
  • Underlying condition
  • Vitamin K iv
  • Replacement clotting factors
  • FFP (Temporary)
  • Half life II, V, VII, IX, X
  • Volume
  • Na Load
  • Platelet infusions
  • Avoid FIX concentrates !! ?? !!
  • Thrombogenic
  • Antifibrinolytics, role in upper GIT bleeding
  • Liver transplant now an option

9
DISSEMINATED INTRAVASCULAR COAGULATION DIC
  • Defibrination Syndrome
  • Consumption Coagulopathy
  • Pathogenesis
  • A trigger (thromboplastic) conditioning
    factors RE block
  • Thrombin generation
  • Intravascular coagulation
  • Clotting factors platelet consumption
  • FV, FVIII, fibrinogen, platelets ?
  • Clinical Settings
  • Childbirth, amniotic fluid embolus
  • Septicaemia, meningococcus,
  • Shock, trauma
  • Incompatible transfusions
  • Anaphylaxis
  • Manifestations
  • Bleeding Bruising

10
DISSEMINATED INTRAVASCULAR COAGULATION
  • Classification
  • Acute Self limiting if correct Rx
  • Chronic Self perpetuating
  • Laboratory Tests
  • FBC Anaemia Tpenia
  • Coagulation PT ? (V ?)
  • APTT ? (VIII ?)
  • Fibrinogen ? D-Dimer ?
  • Fibrinolysis (2ยบ)

11
DISSEMINATED INTRAVASCULAR COAGULATION
  • Acute
  • Therapy Remove trigger
  • Correct conditioning factors
  • Replace deficient factors
  • Triggers Infection, Fetus, Trauma
  • Conditioning factors Hypoxia O2
  • Acidosis HC03
  • Pregnancy
  • Leukaemia (APML)
  • Replace V VIII FFP /or FVIII cone
  • Platelets Platelet infusions
  • Inhibitors ATIII
  • Chronic
  • Therapy Malignant Remove
  • Pre eclampsia Control
  • Chronic infection Correct
  • The debatable role of Heparin in DIC

12
ANTICOAGULANT OVERDOSE
  • Oral anticoagulants Warfarin
  • Mechanism
  • Vitamin K antagonists
  • Inhibit reductase enzyme
  • Vit K epoxide ? Vit K
  • Inhibition of carboxylation of precursors of
  • II, VII, IX, X
  • Cant combine Ca Plipids for coagulation
  • PIVKA
  • Protein induced Vit K absence
  • Precursors. Non COOH

13
ANTICOAGULANT OVERDOSE
  • Oral Anticoagulants - WARFAIN
  • Monitoring
  • Prothrombin Time
  • II, V, VII, X
  • NB Not monitoring FIX
  • INR PR1SI
  • Range INR
  • DVT 2.3
  • PE 2.5 - 3.5
  • Heart valve 3 - 4

14
ANTICOAGULATION OVERDOSAGE
  • Oral Anticoagulants - Warfarin
  • Warfarin Usage Long(er) Term
  • Heart Valve
  • Pulmonary emboli
  • Recurrent DVT
  • Thromboembolic
  • Warfarin Overdose INR gt 5
  • Risk of bleeding
  • Haematoma
  • Haematuria
  • Intercranial
  • Trauma
  • Precipitating Factors Simple overdose. Monitoring
    ?
  • Intercurrent infection
  • Antibiotic use
  • Diet change
  • Analgesics, eg. paracetemol
  • C2H5OH XS

15
ANTICOAGULANT OVERDOSE
  • Heparin
  • Mechanism
  • IV Standard heparin. Short acting (1 1/2 hour)
  • Combine with ATIII
  • Inhibits thrombin, Fibrinogen - Fibrin
  • Not clot bound thrombin
  • Neutralised by PF4 on platelets
  • Value, acute therapy of thrombosis
  • SC LMW Heparin
  • Delayed absorbtion. Smaller doses
  • Prolonged action
  • Specific anti Xa
  • Value in prophylaxis
  • Wider acceptance for therapy
  • Monitor IV or Standard heparin

16
ANTICOAGULANT OVERDOSAGE
  • Heparin
  • Heparin overdose
  • Clinical Usually IV
  • Administered by iv infusion pump
  • Retroperitoneal bleeding - shock
  • Intracranial bleeding
  • Therapy Stop Heparin
  • May administer Prot-SO4
  • Weight for weight neutralisation
  • 1mg P ? 1mg Hep - 100u
  • Average dose - 10mg of Prot-SO4
  • Often expectant Rx
  • Mainly transfusion

17
VITAMIN K DEFICIENCY
  • Mechanism Essential co-factor synthesis of
  • II, VII, IX, X
  • Protein C
  • Protein S
  • Clinical
  • Adults Rare
  • Bowel resection
  • Obstructive jaundice
  • Sick prolonged iv, no suppls
  • Children Neo nat
  • Above
  • Presentation Precipitously
  • Bruising
  • Tissue bleeding
  • Intracranial haemorrhage - neonates

18
CIRCULATING ANTICOAGULANTS
  • FVIII Inhibitors Acquired
  • Lupus like anticoagulant
  • Anti phospholipid syndrome
  • Anti cardiolipid antibody
  • Lab Test Coagulation
  • APTT ? IRN N
  • Mixing ?
  • FVIII ?
  • FVIII Inhibitors
  • Rare
  • Major bleeding problems - subcutaneous
  • Occur Elderly, spontaneous
  • Post partum
  • Autoimmune disorders
  • Rheumatoid arthritis
  • Therapy Difficult - Resistant

19
CIRCULATING ANTICOAGULANTS
  • Lumpus like inhibitor
  • Occurs DLE
  • Other autoimmune disorders
  • Lab Test APTT ? INR N
  • Mixing prolonged
  • Lipids correct
  • Clinical Not usually association with bleeding
  • Thrombotic association, anomolous
  • Therapy Surgery
  • ? LMW heparin
  • Ante Phospholipid Syndrome
  • Recurrent miscarriages

20
ACQUIRED DISORDERS OF PLATELET FUNCTION
  • Thrombopathy Impaired platelet function
  • in vitro ? in vivo
  • Asprin effects Impair ADP release
  • Bruising , bleeding post op
  • Not reversible
  • Cardiac situation
  • Rx May need platelet infusions
  • for surgery
  • Uraemia Renal metabolite not excreted
  • Platelet mal function
  • Bruising bleeding
  • ? Platelet infusion or Cryoprecipitate
  • Paraproteins

21
ACQUIRED DISORDERS OF PLATELET NUMBERS
  • Thrombocytopenia
  • Drug induced. Immune
  • Chemotherapy suppression
  • Drug Induced Quinine/Quinidine
  • Acute Tpenia ? 5x10???
  • Drug as haptene
  • Therapy Stop drugs
  • Steroids
  • HEPARIN INDUCED TPENIA THROMBOSIS
  • 2-3 people with iv Heparin
  • Antibody IgG to PF4 platelet complex
  • Thrombin generation - thrombosis
  • Tpenia
  • Therapy Regular platelet counts
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