Bleeding, thrombosis, and transfusion Flashcards
Life span of platelets
7 to 10 days
Normal platelet count
150 to 400 ⨉ 10^9 /L
Receptors on platelets for adhesion to collagen and platelet aggregation
glycoprotein (GP) receptors
3 Steps in primary haemostasis
platelet adhesion, platelet activation, platelet aggregation
How do platelets adhere to endothelium?
direct adhesion / indirect adhesion through von Willebrand factors (vWF)
Coagulation pathway
Extrinsic pathway: TF + 7 –> + 10. Intrinsic pathway: 2 –> + 5, 8, 11; 11 –> + 9; 9 + 8 –> + 10; 10 + 5 –> + 2; Common pathway: 2 –> + 1; 13 –> stabilise 1
What is TFPI?
Tissue factor pathway inhibitor, which inhibits TF-VIIa complex in extrinsic pathway
Which clotting factors are vitamin K dependent?
2,7,9,10
4 natural anticoagulants and their actions
TFPI –> inhibit TF-VIIa complex in extrinsic pathway; Protein C –> degrade factors 5a, 8a; Protein S –> enhance protein C activity; antithrombin –> suicidal inhibitor of thrombin and factor 10a
Fibrinolysis pathway
plasmin digests fibrin polymers, TPA activates plasminogen, PAI inhibits TPA
What is spurious thrombocytopenia?
falsely low platelet count due to platelet clumps by EDTA / automated blood analyser
Coagulation profile and the respective pathway being assessed
PT (extrinsic pathway), APTT (intrinsic pathway), TT (fibrinogen)
INR formula
(PT(test) / PT(normal))^ISI
Reason for increased PT only
deficiency / inhibitor of factor 7
Reasons for increased APTT only (3)
- deficiency / inhibitor of 8,9,11
- lupus anticoagulant
- heparin
Reasons for increased PT and APTT (4)
- deficiency / inhibitor of 2,5,10
- multiple factor deficiency
- fibrinogen deficiency / disorder
- heparin
Reasons for increased PT, APTT, TT but decreased PLT
DIC, acute liver failure
Method and interpretations of mixing test
Method: mixing patient sample with normal plasma –> measure clotting time
Results: reduced time –> factor deficiency; unchanged time –> factor inhibitors
Differentiate petechiae, purpura and ecchymosis
petechiae (<3mm), purpura (3~10mm), ecchymosis (>10mm)
Differentiate presentations between platelet disorders and coagulopathy
Site, presence of petechiae (platelet), presence of ecchymosis / purpura (coagulopathy), bleeding after cuts (platelet), bleeding after surgery (immediate vs delayed)
Indications for platelet transfusion
PLT <10
Contraindications of platelet transfusion (4)
ITP, SLE, TTP, HUS
Indications for FFP transfusion (2)
TTP, reversal of warfarin overdose
Indications for cryoprecipitate transfusion (3)
vWD, fibrinogen deficiency, factor 13 deficiency
Mechanism of DDAVP
increase release of vWF from endothelium
Haematological indications (2) and side effects (3) of DDAVP
indications: vWD, mild haemophilia A; side effects: water retension, flushing, headache
What is Novoseven and its indications?
recombinant FVIIa. Indications: haemophilia, factor 7 deficiency
Mechanism of action of Tranexamic acid
inhibit conversion of plasminogen to plasmin to reduce fibrinolysis
MC cause of isolated thrombocytopenia
ITP
Pathogenesis of ITP
autoAb coats platelets –> destroyed in spleen; autoAb coats megakaryotes –> destroyed prematurely in BM
Diagnosis of ITP
exclusion of secondary causes
Treatment of ITP: first line (2) and second line (2)
First line: steroid, IVIG; Second line: TPO mimetics, splenectomy
TPO mimetics (2)
Eltrombopag, Romiplostim
Pathogenesis of drug-induced thrombocytopenia purpura
drugs bind to GP-R of platelets –> recognised by IgG
(For heparin, IC is formed, and platelets could be activated and cause thrombosis)
Treatment of drug-induced thrombocytopenia purpura
stop offending drugs, platelets
Aetiology of DIC (5)
Obstetrics, Malignancy, Infection, Trauma, HSR
Pathogenesis of DIC
pathologically increase thrombin –> widespread intravascular consumption of platelets, clotting factors, fibrin –> bleeding
Blood test results in DIC (6)
↑ PT, APTT, TT; ↓ Plt; ↑ D-dimer, ↓ fibrinogen
What is D-dimer?
degradation products of cross-linked fibrin plugs
Management of DIC
treat underlying cause, supportive: platelets, FFP, cryoprecipitate
Pathogenesis of TTP
lack of ADAMTS13 –> ↑ vWF –> thrombi formation
Presentations in TTP (5)
(FAT RN) Fever, MAHA, Thrombocytopenia, Renal impairment, Neurological symptoms
Management of TTP
FFP
Pathogenesis of HUS
E. coli O157:H7 –> produce verotoxin that destroy endothelial wall –> platelet aggregation [esp. renal vessels]
vWD screening tests (3)
vWD antigen, vWD:RCo (ristocetin cofactor), Factor VIII activity
Management of vWD
cryoprecipitate, DDAVP
Haemophilia hereditary pattern
XR
Types of haemophilia
A (factor VIII deficiency), B (factor IX deficiency)
Severity levels of haemophilia (3)
6~30%: mild (bleeding after surgery / trauma), 1~5%: moderate (bleeding with mild injury), <1%: severe (spontaneous bleeding)
Management of haemophilia (3)
factor concentrates replacement, Novoseven, DDAVP (type A only)
Virchow’s triad (3+6+3)
(1) Stasis (immobility, venous insufficiency, obesity); (2) Hypercoagulability (malignancy, pregnancy, oestrogen, dehydration, myeloproliferative diseases, APS) ; (3) Endothelial injury (surgery, trauma, indwelling catheter)
What is antiphospholipid syndrome (APS)?
autoimmune hypercoagulable state caused by antiphospholipid antibodies
Presentations of APS
recurrent arterial / venous thrombosis, recurrent miscarriage
Antiphospholipid antibodies (3)
lupus anticoagulant, anti-Cardiolipin Ab, anti-β2-glycoprotein-1 Ab
Management of APS
warfarin (INR: 2.5~3.5)
Homan sign
pain illicited by forceful leg dorsiflexion –> indicate DVT
Presentations of DVT
LL swellling and tenderness, pitting oedema, superfical vein dilatation, Homan sign
Diagnosis of DVT (3)
Doppler USG, Contrast venogram, D-dimer
What will be observed in Doppler USG of a DVT patient?
no phasic pattern
PE aetiology
venous thromboembolism (MC), right ventricular thrombus, paradoxical embolism, septic emboli…
Presentations of PE (3)
acute breathlessness, haemoptypsis, chest pain
Risk stratification system for PE to determine the need for CT pulmonary angiogram
Wells score
Investigations for PE (3)
D-dimer, CT pulmonary angiogram, ventilation perfusion scan (obsolete)
Compare UFH and LMWH
UFH: anti-platelet effect, IV, monitor by APTT, ok for pregnancy, renal impaired patients; LMWH: more anti-Xa effect, SC, monitor by FXa assay, fewer side effects
Mechanism of Warfarin
inhibit of vitamin K epoxide reductase –> ↓ reduced vitamin K –> - γ-glutamyl carboxylase —> cannot activate clotting factors 2,7,9,10 —> - clotting factors 2,7,9,10
Target INR for Warfarin intake in (1) DVT, PE, AF; (2) Mechanical heart valves; (3) recurrent VTE
(1) 2.5; (2) 2.5~3.5; (3) 3.5
DDI of Warfarin (3)
99% albumin binding; NSAIDs, aspirin –> ↑ bleeding risk; antibiotics –> ↑ efficacy
Warfarin overdose management (4)
withhold warfarin, vitamin K, FFP, prothrombin complex concentrate (PCC)
Reversal agent for dabigatran
Idarucizumab (“DA”bigatran) 依達露茲
Fibrinolytic agents (2)
r-TPA, streptokinase
Transfusion triangle for correct patient identification
Patient wristbnad, Request form, Sample tube
Type of variance of blood group antigens and examples (3)
whole molecule (RhD); single monosaccharide (ABO); single AA
2 types of blood group antigens (class, examples)
naturally occurring (IgM, anti-A anti-B) v.s. immune-related (IgG, anti-D, develop after exposure)
Pathogenesis of haemolytic disease of newborn (HDN)
in a RhD- mother, labour / prenatal bleeding for a RhD+ fetus will sensitise the mother to produce anti-D IgM –> on subsequent pregnancy, exposure to fetal RhD+ will produce anti-D IgG, which attacks red cells in fetus
Pre-transfusion compatibility testing (3)
Blood typing (forward / cell –> reverse / serum) –> Antibody screening –> Cross-matching
Which blood product requires continuous agitation during storage?
Platelets
Storage temperature and shelf life of blood products (6)
Storage temperature: whole blood & red cells 2~6°C, platelets & leukocytes 20~24°C, FFP & cryoprecipitate -30°C
Shelf life: whole blood 35 days, red cells 42 days, leukocytes 1 day, platelets 5 days, FFP & cryoprecipitate 1 year
Which blood product should be given for children to replenish blood loss?
Plasma methylene blue treated
Transfusion: adverse event definition
an undesirable and unintended occurrence
Transfusion: error definition
deviation from standard procedure
Transfusion: near miss definition
error that is discovered before the start of transfusion
Transfusion: incident definition
error that leads to mis-transfusion
Transfusion: adverse reaction definition
undesirable response in a patient
Adverse transfusion reaction: Severity versus Imputability
4 grades (non-severe to death) to 5 levels (excluded to definite)
Acute transfusion reactions definition
adverse reactions within 24 hours of transfusion
Acute management before blood results come back in acute transfusion reaction (5)
- Stop transfusion immediately –> save the blood units & blood giving set for investigation
- Use a new giving set and keep vein open with normal saline
- Clerical check for compatibility between recipient and blood units given
- Maintain blood pressure with IV colloid solutions
- Monitor urine output, give diuretics to maintain adequate urine output
Aetiology of acute transverse reactions (6)
- Allergic transfusion reaction
- NFHTR
- Septic reaction
- AHTR
- TRALI
- TACO
Management of allergic transfusion reaction (2)
IV chlorpheniramine, IV steroids
Pathogenesis and management of FNHTR
(Febrile non-haemolytic transfusion reaction)
Pathogenesis: recipient Ab –> + donor leukocytes –> release cytokines
Management: paracetamol (restrat infusion of the same unit if mild)
MC blood product that causes septic reaction
platelets
Management of septic reaction
septic workup, IV Tazocin, report to blood bank
Major vs minor blood group incompatibility
Major: recipient Ab attack donor RBCs
Minor: Donor Ab attack recipient RBCs
Pathogenesis of AHTR
IgM recognise foreign blood group Ags –> complement activation that forms MAC –> intravascular haemolysis
complement –> endothelial damage –> DIC
Management of AHTR
fluid resuscitation + monitor electrolytes
Pathogenesis and presentations (2) of TRALI
Pathogenesis: donor Abs –> attack recipient’s lungs
Presentations: respiratory distress, fever
Presentations of TACO (2)
volume overload, respiratory distress
Aetiology of delayed transfusion reactions (5)
- Delayed haemolytic transfusion reactions
- Post-transfusion pupura
- Transfusion-associated graft-versus-host disease
- Transfusion-transmitted infection
- Transfusion-related haemosiderosis
Pathogenesis and presentations of delayed haemolytic transfusion reactions
patient Abs destroy donor RBCs
failure to respond adequately to transfusion
Pathogenesis of post-transfusion purpura
patient Abs –> destroy donor platelets –> destroy own platelets via collateral damages
Pathogenesis of transfusion-associated graft-versus-host disease
donor T cells –> attack recipient BM
Alternatives to transfusion (3+3)
Pharmacological: oral iron, EPO, anti-fibrinolytics
Autologous blood transfusion: predeposit autologous blood, intraoperative cell salvage, postoperative cell slavage
3 pillars of patient blood management
- Optimise red cell mass
- Minimise blood loss
- Manage tolerance to anaemia
2 Aims of patient blood management
- Improve patient outcomes
- Reduce demands for blood products
Restrictive transfusion strategies definition
transfusion of the right number of units of blood to the right patient at the right time, in the right conditions, and according to appropriate guidelines
What is Evans syndrome?
autoimmune thrombocytopenia (ITP + AIHA)
Difficulties in compatibility testing in patients with AIHA
- recipient autoAb may react with normal RBCs —> FP
- recipient autoAb may mask RBC alloAb
Mechanism of action of heparin
+ anti-thrombin III –> - factor IIa, Xa
Antidote for heparin
Protamine
How does PE lead to death?
obstructive shock –> Right heart failure
hypoxia / respiratory failure
