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 (2º)

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