Lecture 15- Acquired Bleeding Disorders Flashcards
1
Q
Platelet type bleeding
A
- skin, mucous membranes (epistaxis, gums, vaginal, GI)
- cuts bleed
- petechiae
- ecchymoses small and superficial
- haemarthrosis rare
- bleeding after surgery is immediate and mild
2
Q
Clotting factor type of bleeding
A
- site: deep, in soft tissues (joint + muscle)
- cuts dont bleed
- no petechiae
- large, deep ecchymoses
- comon haemarthrosis, muscle bleeding
- bleeding after surgery is delayes and severe
3
Q
Investigating an ABD
A
- FBC (platelet count)
- APTT
- PT (INR)
- Fibrinogen
- D-dimers (fibrin generation)
- thrombin time
4
Q
Tests of hemostasis: PT
A
- PT tests extrinsic and common pathways
- prolonged in disorders affecting factors 7,10,5,2 and 1 (fibrinogen)
- liver disease, vit K, warfarin therapy, common pathway deficiency
5
Q
Tests of hemostasis: APTT
A
- tests intrinsic and common pathways
- prolonged in disorders affecting 8,9, 10, 12, 11, 5, 2 and I (fibrinogen)
- Haemophilia A and V, vwf disease
- inhibitors: heparin, lupus anticoagulant
- severe liver disease/ Vit K deficiency
- deficiency factor 11 and 12
- common pathway deficiency rare
6
Q
- Causes of thrombocytopenia
A
- laboratory artefact
- increased destruction: immune, drug-induced, DIC, dilutional (massive transfusion)
- sequestration: splenomegaly
- decreased production: generalised BM failure due to chemo, drugs, malignancy, alcohol toxicity
7
Q
What level of thrombocytopenia causes bleeding
A
- spontaneous bleeding: plat
8
Q
Causes of increased platelet destrictiuon
A
- immune idiopathic thrombocytopenic purpura (ITP)
- other immune causes: autoimmune disease (SLE), drugs (HITTS), malignancy associated antibodies (CLL)
- Viruses: EBV, HIV
- alloimmune (post-transfusion)
- disseminated intravascular coagulation (DIC)
- thrombotic thrombocytopenic purpura (TTP)
9
Q
Acute ITP
A
- more in kids
- treat with steroids, IVIG, splenectomu
10
Q
Chronic ITP
A
- more common in adults
- usually idiopathic
- SLE, HIV, CLL, autoimmune hemolytic anemia
11
Q
Diagnosis of ITP
A
- plat
12
Q
HITTS and TTP
A
- not commonly associated with bleeding
- associated with thrombosis despite low platelet counts
- HITTS: antibodies complex with heparin and PF4, increased destruction but also platelet activation
- TTP: congenital or acquired deficiency of VWF cleaving enzyme, fragmentary haemolysis, microvascular effect
13
Q
Two questions to ask when your patient has low platelets
A
- have they been exposed to heparin recently (HITTS)
- are there red cell fragments on this film and a haemolytic anaemia (TTP)
- speak to hamaematologist urgently: these patients are at risk of clotting, not bleeding
14
Q
Platelet function disorders
A
- inherited: membrane defects: bernard-soulier syndrome, Glanzmann thromasthenia
- acquired: myelodysplasia, myeloproliferative disorders, ureamia, drug (aspirin, clopidogrel, NSAIDS)
- garlic, ginger, gingko
15
Q
How are coagulation factors produced
A
- Liver synthesizes 1,2,5,7,9,10,11 as well as the natural anticoagulants protein C, S and antithrombin III and thrombopoietin, which stimulates megakaryocyte production in BM
16
Q
Vit K dependent factors
A
- II (prothrombin)
- VII, IX, X, Protein C, Protein S
- Gla-rich tail domains anchor factors to membrane
17
Q
Vit K source
A
- green leafy vegetable
18
Q
Vit K metabolism
A
- Dietary Vit K is portein bound
- released by pancreatic enzymes
- Bile salts then solubilize it into micells
- absorbed and incorporated into chylomicrons
- transported to liver
19
Q
Acquired coagulation disorders:
A
- Impaired production- liver disease, vit K deficiency
- Increased destruction (or clearance): disseminated intravascular coagulation, massive transfusion, inhibitors
- dysfunction: anticoagulant drugs - heparin, warfarin, direct oral anticoagulants
20
Q
AcqHemostasis test in acquired bleeding disorders: liver disease
A
- Platelets low
- PT prolonged
- APTT prolonged
- TT normal
21
Q
Hemostasis tests in acquired bleeding disorders: DIC
A
- platelets low
- PT prolonged
- APTT prolonged
- TT very prolonged
22
Q
Hemostasis test in acquired bleeding disorders: Massive transfusion
A
- platelets low
- PT prolonged
- APTT prolonged
- TT prolonged
23
Q
Hemostasis test in acquired bleeding disorder: heparin
A
- platelet normal
- OT normal
- APTT prolonged
- TT prolonged
24
Q
Hemostasis test in acquired bleeding disorder: lupus anticoagulant
A
- platelet normal
- PT Normal or prolonged
- APTT prolonged
- TT normal
25
How can we tell if coag tests are abnormal due to a factor deficiency or an inhibitor (antibody)?
- mixing studies
- Aka: correction tests using APTT or PT
- used if unexplained prolongation APTT or PT, mix patient plasma with normal plasma
- correction = factor deficiency
- if no correction of APTT: inhibitor
26
Misleading mixing studies
- weak LAC
| - time dependent inhibitors (eg: G8)
27
Inhibitors of coag factors
- usually antibodies
- idiopathic or occur in immune disorders, associated with malignancy, in pregnancy or postpartum
- occur in inherited factor deficiencies as a complication of treatment
- directed against: F8, VWF, 9, 10, 5, 13, fibrinogen
- or non specific: lupus anticoagulant, paraprotein
28
Causes of bleeding in liver disease
- impaired synthesis clotting factors
- thrombocytopenia (BM suppression, hypersplenism)
- increased fibrinolysis: decreased clearance of plasminogen, activators, decr synthesis antiplasmin, platelet dysfunction contribution
- dysfibrinogenemia
29
Contributing factors for coagulopathy
- hypothermia
- hypotension
- hypocalcemia/citrate toxicity
- dilutional factor and platelet deficiency
- liver damage/dysfunciton/hypoxia
- disseminated intravascular coagulation
- transfused products
30
Management of massive blood transfusion and coagulopathy
- good resucitation: restore perfusion
- keep worm
- fresh frozen plasma and platelets according to test result
- cryoprecipitate if low fibrinogen
- antifibrinolytics
- distinguish surgical bleeding from coagulopathy
- factor 7a
31
When clotting leads to excessive bleeding: DIC
- inappropriate and excessive activation of coagulation
- consumption of platelets and coagulation factors: thrombocytopenia, prolonged coag test, bleeding
- consumption of anticoagulant and fibrinolysis factors: thrombosis, fibrin deposition, and end-organ damage
32
Causes of DIC
- severe infection
- malignancy: APML, leukemia, metastatic
- obstetric: IUFD, placental abruption
- shock
- liver disease/failure
- transplantation - organ rejection
- extra-corporeal circulation: Cardiac bypass
- extensive intra-vascular hemolysis - ABO incompatible transfusion
- snake bite
- vascular malformations
33
Disseminated intravascular coagulation
- Diagnosis: clinical setting and signs of generalised bleeding, including IV lines and puncture sites
- coagulation: low platelets, prolonged APTT, PT, TT, low fibrinogen, Raised D-dimer, fragments of red cells on blood filmn
34
Treatment of DIC
- remove or treat cause
- adequate resuscitaiton
- fresh frozen plasma and platelets
- monitor with test results
- surgical management or delivery of baby
- cryoprecipitate especially if low fibrinogen
- surgical management or delivery of baby
- Heparin only in selected cases: amniotic fluid embolism, foetal death in utero
35
Blood vessels pb with coagulation
- vasculitis
- connective tissue disorders
- steroids
- senile purpura
36
Types of purpura
- palpable purpura: vasculitis, allergic purpura, fibrin activation in subcutaneous tissue
- non-palpable purpura: small bruises, red cell leakage into tissues (eg: senile pupura)
37
Fibrinolysis
- primary fibrinolysis is really fibrinogenolysis
- excessive activation of plasminogen
- causes: trauma, tumours (prostate, pancreas, lung, brain)
- may be therapeutic
