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MBBS VI - SpC - Medicine > Haematology - Clotting disorders > Flashcards

Haematology - Clotting disorders Flashcards

1
Q

3 stages of blood clot

A

□ Vasoconstriction from loss of normal vasodilator secretion of intact endothelium (eg. PGI2, NO)

□ 1o haemostasis: collagen exposure and loss of endothelium → triggers platelet activation → formation of platelet plug (unstable)

□ 2o haemostasis: activation of coagulation cascade → culminating in fibrin production → cross-link with platelet plug → producs stable fibrin clot followed by clot retraction and fibrosis healing

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2
Q

Agonists of platelet activation

A

Agonists:
→ Collagen from subendothelial structures
→ Thrombin from coagulation cascade
→ ADP, adrenaline, serotonin, calcium ionophore from platelet degranulation

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3
Q

Phases of platelet activation

A

Phases of activation:
Trigger: platelet activation agonist → ↓cAMP → ↑intracellular [Ca]
Shape change in cytoskeleton → open canalicular system ‘flips outward’ to provide large SA for coagulative cascade
Platelet aggregation by surface glycoproteins
Platelet degranulation → further ↑activation → +ve feedback

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4
Q

Function of degranulation and platelet aggregation

A

Granule contents:

Specific α-granules contain activators of coagulative cascade, eg. fibrinogen, factor V and XI, vWF, HMWK

Electron-dense (δ) granules contain platelet activation agonists, eg. ADP, ATP, serotonin, calcium

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5
Q

Function of platelet surface glycoproteins

A

Surface glycoproteins (GP): act as receptors for platelet adhesion/aggregation

Glycoprotein Ia/IIb and VI → mediates direct adhesion to collagen

Glycoprotein Ib → mediates vWF-dependent adhesion to collagen

Glycoprotein IIb/IIIa → mediates vWF-dependent aggregation and association with fibrinogen

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6
Q

Outline the in-vivo cascade of coagulation

A
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7
Q

Two physiological phases of coagulation cascade in vivo

A

Initiation phase and Amplification phase

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8
Q

2 metrics to measure coagulation cascade

A

Prothrombin time (PT)
→ Activates coagulation cascade via extrinsic pathway
→ Measures activity of factor 7, Tissue Factor

Activated partial thromboplastin time (aPTT):
→ Activates coagulation cascade via intrinsic pathway
→ Measures activity of factor 8,9

Factor 10 is the final common pathway

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9
Q

Vascular defects causing bleeding disorder

A

Congenital vascular defects

  • Hereditary haemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease)
  • Ehler-Danlos syndrome

Acquired vascular defects

  • Purpura simplex in young ladies
  • Senile purpura in those >65y (UL>LL due to sunlight exposure)
  • Scurvy due to vitamin C deficiency
  • Steroid purpura
  • Vasculitis, eg. Henoch-Schönlein purpura
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10
Q

Congenital platelet defects

A

Qualitative, i.e. platelet dysfunction

  • Defects of adhesion: *Bernard-Soulier syndrome (GPIb-IX defect)
  • Defects of aggregation: Glanzmann’s thrombasthenia (GPIIb/IIIa defect)
  • Defects of degranulation: Gray platelet syndrome (α-granule deficiency)
  • Storage pool disease (δ-granule deficiency)

Quantitative, i.e. congenital thrombocytopenia

  • Bernard-Soulier syndrome: thrombocytopenia with giant platelets
  • Wiskott-Aldrich syndrome: cytoskeleton mutation with immunodeficiency
  • May-Hegglin anomaly: giant platelets with Dohle body-like neutrophilic inclusions due to myosin heavy chain mutation
  • Congenital BM failure syndromes
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11
Q

Acquired platelet defects

A

Qualitative:

  • Antiplatelet drugs: aspirin, P2Y12 inhibitors, GPIIb/IIIa inhibitors, NSAIDs
  • Uraemia (common):
    (1) Uraemia → ↑NO production inhibit platelets
    (2) Anaemia → altered blood rheology → ↓platelet contact with endothelium
  • MPN ± ↑PLT: platelet dysfunction due to platelet absorption of vWF

Quantitative:
↓production due to BM pathologies (e.g. Aplastic anaemia, Marrow infiltrative disease)

↑destruction: (e.g. Immune thrombocytopenic purpura (ITP), Drug-induced thrombocytopenia, Post-transfusion purpura, DIC and thrombotic microangiopathies (mixed)), Hypersplenism

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12
Q

Congenital coagulation defect

A
  • Von Willebrand disease (vWD)
  • Haemophilia A due to factor VIII deficiency
  • Haemophilia B due to factor IX deficiency

Other very rare diseases (majority AR inheritance)
Factor VII deficiency → isolated ↑PT
Factor X deficiency → ↑PT + ↑aPTT
Fibrinogen deficiency → ↑PT, aPTT, TT
(Factor XII deficiency → isolated ↑aPTT)

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13
Q

Acquired coagulation defects

A

Vitamin K deficiency
- Cholestasis
- Hospitalized patients with malnutrition, malabsorption and Abx use (↓intestinal flora vitamin K production)
- Haemorrhagic disease of the newborn - HDN

Anticoagulant use
- Warfarin, DOAC, Heparin, LMWH

Liver disease with ↓production of clotting factors

DIC and thrombotic microangiopathies

Massive transfusion

Acquired inhibitors of coagulation: Acquired haemophilia A due to anti-factor VIII Ab; Acquired von Willebrand syndrome (aVWS)

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14
Q

How to differentiate between platelet disorder and coagulation disorder?

A

Platelet type: mucocutaneous bleeding (petechiae/purpura, epistaxis, tongue haematoma, GI bleed, menorrhagia) or continuous oozing after trauma

Coagulation type: deep-seated bleeding (muscle haematoma, haemarthrosis, ICH, retroperitoneal haematoma) or rebleeding after initial cessation

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15
Q

3 types of subcutaneous bleed with size cut-offs

A
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16
Q

Key questions in bleeding history

A

Pattern of current bleeding:
→ Platelet type: mucocutaneous bleeding (petechiae/purpura, epistaxis, tongue haematoma, GI bleed, menorrhagia) or continuous oozing after trauma
→ Coagulation type: deep-seated bleeding (muscle haematoma, haemarthrosis, ICH, retroperitoneal haematoma) or rebleeding after initial cessation

Prior/other bleeding:
→ Age of onset: congenital vs acquired, previous blood screening results
→ Previous bleeding challenges, eg. labour, surgery, dental procedures, injury
→ Other bleeding: head-to-toe bleeding history → ICH, epistaxis, gum bleeding, easy bruising or cutaneous petechiae/purpura, joint/muscle haematoma, GI bleeding, menstrual Hx

Systemic illnesses, eg. liver disease, kidney disease, connective tissue disease

Drug history esp on oral anticoagulant, fibrinolytic and antiplatelet use

Family history of clotting disorders: inherited vs sporadic/acquired

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17
Q

Outline physical examinations for abnormal bleeding

A

Physical examination: look for features of suspected conditions
Cutaneous: initially red/purple and later becoming yellow as haemoglobin is degraded
→ Bleeding: petechiae (<2mm, esp dependent areas), purpura (2-10mm), ecchymosis (>10mm)
→ Telangiectasiae around lips/fingertips → indicate HHT
→ Hyperelasticity → indicate Ehler-Danlos syndrome

Fundoscopy: retinal bleeding indicates ↑risk for CNS bleeding

Mouth: for gum bleeding and macroglossia (classical for amyloidosis)

Joints: for joint effusion (haemarthrosis) and deformities (chronic haemarthrosis)

LNs: for haematological malignancies

Abdomen:
→ Hepatosplenomegaly in liver disease, lymphoma, myeloproliferative neoplasm
→ Flank/abdominal mass may be retroperitoneal or abdominal haematoma respectively

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18
Q

Standard investigations for abnormal bleeding

A

CBC ± PBS for platelet count and platelet morphology

Clotting profile including PT and INR, aPTT (± TT)

Additional tests:
→ Platelet function tests and vWF function assay (Normal initial tests)
→ Specific clotting factor assays and mixing tests (haemophilia)
→ Fibrinogen, D-dimer (DIC or thrombotic microangiopathies)

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19
Q

Causes of thrombocytopenia with pancytopenia

A

Marrow hypoplasia*

  • Congenital BM failure syndromes, eg. Fanconi anaemia, dyskeratosis congenita
  • Aplastic anaemia (idiopathic and secondary)
  • Transfusion-associated GvHD

Marrow infiltration*

  • Myelofibrosis (primary, secondary)
  • Malignant infiltration (haematological, non-haematological)
  • Lysosomal storage disease, eg. Gaucher’s disease

Megaloblastic anaemia*

Infections
Sepsis-related haemophagocytosis (HLH) and BM suppression

Hypersplenism*

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20
Q

Platelet counts and bleeding risk

  • Surgical bleeding
  • Spontaneous bleeding
  • Life-threatening bleeding
A

<100×109/L → risk of surgical bleeding for high-risk operations, eg. major cardiac or orthopaedic surgery, neurosurgery

<50×109/L → risk of surgical bleeding for usual operations

<20×109/L → risk of spontaneous bleeding

<10×109/L → risk of life-threatening bleeding, eg. ICH

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21
Q

Investigations for thrombocytopenia

A
  1. Repeat CBC (± use citrate tubes) to r/o platelet clumping
    → Pseudothrombocytopenia may occur esp with EDTA tubes
  2. PBS: r/o platelet clumping, morphological abnormalities
    → Giant platelet in peripheral destruction (eg. ITP) or congenital megathrombocytopenia (eg. Bernard-Soulier)
    → Large, agranular platelets in grey platelet syndrome (no α-granules)
    → RBC/WBC morphology, eg. schistocyte in MAHA, megaloblastic anemia
  3. Consider BM failure if pancytopenia
    → Bone marrow exams
  4. Consider peripheral destruction if isolated thrombocytopenia
    → Hypersplenism with chronic liver disease → LFT
    → ITP or drug-induced thrombocytopenia → PBS + r/o alternative causes by HIV, HCV
  5. Assess bleeding risk → PLT count + fundus for risk of Intra-cranial hemorrhage
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22
Q

Treatment of thrombocytopenia (Non-ITP)

various level of treatment e.g. actively bleeding vs prevention of spontaneous bleeding

A

Platelet concentrate transfusion
for Active bleeding:
- <50×109/L if diffuse microvascular/mucosal bleeding, major bleeding
- <100×109/L if retinal/CNS bleeding or post-cardiopulmonary bypass bleeding

for Prevention of spontaneous bleeding: <10×109/L if stable, <20×109/L if fever/sepsis

for Preparation of invasive procedure:
- <20×109/L for minor procedures, eg. diagnostic endoscopy, central line, BM aspiration
- <50×109/L for major procedures
- <100×109/L for neurosurgery or ocular surgery

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23
Q

Contraindications of Platelet concentrate transfusion

A

ITP
TTP/ HIT
Antiplatelet drug use

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24
Q

Investigations for suspected hereditary platelet dysfunctions

A

Platelet aggregometry: measure response to agonists by aggregometry

PFA-100: platelet function analyzer

Electron microscopy studies: can detect granulation disorders

Flow cytometry: can detect glycoprotein defects

Genetic studies as indicated

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25
Q

ITP

- Types and definition

A

Primary ITP: acquired immune-mediated thrombocytopenia (platelet <100×109/L) that is not triggered by apparent associated condition

Secondary ITP: acquired immune-mediated thrombocytopenia a/w underlying condition

Drug-induced immune thrombocytopenia (DITP): thrombocytopenia due to drug-dependent platelet antibodies that cause platelet destruction

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26
Q

Pathogenesis of ITP

A

anti-platelet antibodies leading to platelet destruction

  1. Inciting event: occurs in some cases
    Viral infection: Ab vs viral Ag cross-react with normal platelet antigens → molecular mimicry
    Immune diseases: A/I disease or low-grade lymphoproliferative neoplasm or immunodeficiency → loss of peripheral tolerance → produce autoAb
  2. Antibody production:
    Driven by CD4+ helper T cells reacting to platelet surface glycoproteins
    Results in production of autoAb (usu IgG) vs platelet surface components esp GPIIb/IIIa and GPIb/IX
  3. Consequence: ↓platelet lifespan from ~7-10d to ~1-2d
    Platelet sensitization → premature removal by RES
    Inhibition on TPO stimulation of platelet production in BM
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27
Q

Clinical features of ITP

A
  1. Preceding events: e.g. viral infection
  2. Platelet-type bleeding: petechiae and purpura on skin and mucosa
  3. Thrombocytopenia: <100×109/L, ↑risk of bleeding if platelet <20×109/L
  4. Fatigue

± anaemic S/S: usu due to bleeding (IDA)
± hemolysis: Evans syndrome = AIHA + ITP; Thrombotic microangiopathies (TMA): MAHA or TTP

28
Q

Diagnostic criteria of Primary ITP

A

Diagnosis by EXCLUSION:

  1. isolated thrombocytopaenia (<100×109/L) w/o anaemia, leukopenia or apparent cause of thrombocytopenia
  2. Occasional large platelets w/o morphological abnormalities → indicates active thrombocytogenesis

Exclude following:

  • secondary causes of ITP: recent viral infection (esp HCV, HIV), A/I diseases, lymphoproliferative disease
  • causes of peripheral consumption: liver disease and hypersplenism, MAHA, recent transfusion
  • drug use
29
Q

Investigations for suspected ITP

A

CBC: isolated thrombocytopaenia
PBS: occasional large platelets w/o morphological abnormalities

Anti-HIV, HCV if appropriate (inciting viral infection)

Autoimmune profile and aPTT for underlying A/I diseases

Antiplatelet Ab (MAIPA test) (Poor sensitivity)

Bone marrow exam: Rule out MDS

30
Q

Causes of drug-induced thrombocytopenia by BM suppression

A
31
Q

Causes of drug-induced thrombocytopenia by immune reactions

A
32
Q 
Management of ITP
General 
Indication for observation only 
Indications for standard therapy: 1st line and 2nd line
Emergency treatment options
A

General: for secondary ITP
- **Remove inciting drug **
- Treat underlying infection (e.g. HCV, HIV, H. pylori)
- Avoid aspirin and antiplatelet agents, IM injections

For asymptomatic/ minor mucocutaneous bleed: Active Observation: platelet ≥30×109/L

1st line therapy/ significant bleeding: platelet <30×109/L
- **Glucocorticoids: Prednisolone **
- Azathioprine for refractory pt. or prolonged use

2nd line treatment: Steroid-dependent or unresponsive ITP
- Splenectomy
- Rituximab
- TPO receptor agonist: eg. eltrombopag, romiplostim

Emergency therapy
- IVIg (MoA: saturates phagocyte Fc receptors in RES → ↓platelet degradation)
- Pulse IV steroids (methylprednisolone) or oral steroids (pulse dexamethasone)
- IV anti-Rh(D)
- Platelet transfusion

33
Q

Heparin-induced thrombocytopenia

Types and definition, causes of each type

A

HIT type I (10-20%): mild, transient thrombocytopenia occurring in 1-4d after starting heparin
» Non-immune platelet aggregation, clinically insignificant

HIT type II (1-3%): significant thrombocytopenia occurring 5-10d after starting heparin
» Antibody vs platelet factor 4 complexed to heparin&raquo_space; Immune-mediated platelet activation&raquo_space; paradoxical thrombosis with thrombocytopenia

34
Q

Clinical manifestation of Heparin-induced Thrombocytopenia (HIT)

Onset
Platelet levels
Complications

A

thrombocytopenia + paradoxical A/V thrombosis

  • Onset: generally 5-10d
  • Thrombocytopenia (75-90%): mean PLT at 60×10^9/L
  • Thrombosis (up to 50%):
    → VTE and death
    → Skin necrosis esp at site of heparin injection (classical)
    → Acute limb ischaemia
    → Organ ischaemia: stroke, MI, mesenteric, renal
  • Anaphylactoid reaction (rare)
35
Q

Diagnostic criteria of Heparin-induced Thrombocytopenia

A

Clinical: as in 4T score

  • Thrombocytopenia score
  • Timing of platelet count score
  • Thrombosis or other sequalae
  • Other causes of thrombocytopenia

Anti-PF4-heparin antibody demonstrated in serum

36
Q

Management of Heparin-induced Thrombocytopenia

A
  • Stop heparin immediately to halt platelet activation
  • Hold and reverse warfarin: initial warfarin administration depletes functional protein C/S&raquo_space; transient hypercoagulable state

Therapeutic anticoagulation: prevent thrombosis:

  • Parenteral direct thrombin inhibitors, eg. argatroban, bivalirudin
  • Heparinoid anticoagulants, eg. danaparoid, fondaparinux (no interaction with PF4)
  • NOACs, eg. dabigatran, apixaban, edoxaban, rivaroxaban

bridge to warfarin when PLT >150×109/L

37
Q

List all metrics in typical clotting profile

A

Prothrombin time (PT)

International normalized ratio (INR)

Activated partial thromboplastin time (aPTT)

Thrombin time (TT)

Fibrinogen

D-dimer

38
Q

Prothrombin time

  • Function
  • Method
  • Normal range
A

Prothrombin time (PT): clinically used to measure factor VII activity
→ Method: measures time for plasma to clot when exposed to tissue factor
→ Normal range: 11.3-13.5s

39
Q

INR

  • Function
  • Method
  • Use
  • Range
A

International normalized ratio (INR): used to standardize PT assay for therapeutic monitoring
→ Method: calculated from comparison to PT of control serum and ISI (specified in lab assay)

Use:

  • therapeutic monitoring of warfarin
  • surrogate for PT esp in liver failure

healthy people: INR of 1.1 or below is normal
Warfarin use for prophylaxis against thrombosis: INR range of 2.0 to 3.0

40
Q

aPTT

  • Function
  • Method
  • Use
  • Normal range
A

Activated partial thromboplastin time (aPTT): clinically used to measure factor VIII, IX activity

→ Method: measures time for plasma to clot when exposed to thromboplastic material without tissue factor activity (i.e. partial thromboplastin) and negatively charged substance resulting in factor XII activation

→ Note: also used for heparin monitoring as heparin interferes with PT assay

→ Normal range: 25.9-33.7s

41
Q

Thrombin time

  • Function
  • Method
  • Normal range
A

Thrombin time (TT): clinically used as a surrogate for fibrinogen activity
→ Method: measures time for plasma to clot when exposed to thrombin
→ Normal range: 14-19s

42
Q

Fibrinogen level

  • Function
  • Use
  • Normal range
  • Limitation
A

Fibrinogen: precursor to fibrin

Decreased due to ↓synthesis (liver disease) or ↑consumption (widespread thrombosis, eg. DIC, TTP)

Normal range: 1.46-3.38g/L

also an acute phase reactant (APR) → can be falsely -ve

43
Q

D-dimer

  • Function
  • Use
  • Normal range
A

D-dimer: one of the major fibrin degradation products after cleavage by plasmin, also APR

Increased in significant thrombosis, eg. DIC, PE, DVT

Normal range: <0.5mg/L

44
Q

Mixing test for abnormal bleeding

  • Indication
  • Rationale
  • Method
A

Mixing test to differentiate between factor deficiency and factor inhibitor

Indication: in unexplained abnormal clotting time
Rationale: 50% clotting factor activity sufficient for normal clotting

Method: repeat the abnormal test with 1:1 mix with normal plasma (immediate + 1-2h incubation)
→ clotting time normalized in factor deficiency vs abnormal in inhibitor

45
Q

Causes of clotting factor inhibition

A
  • Anticoagulant use, eg. heparin, NOAC (NOT warfarin → ↓synthesis)
  • Lupus anticoagulant: dRVVT/aPTT fails to correct after mixing, but corrected after addition of excess phospholipids
    → only interferes with the test, not in vivo clotting
    → a/w thrombosis not bleeding
  • Acquired Ab vs clotting factors: common in haemophilia
46
Q

Specific Tests for haemophilia and vWD

A

□ Specific factor assay for factor deficiencies, eg. haemophilia A/B, factor XI deficiency

□ vWF assay for suspected von Willebrand disease (vWD)

47
Q

Causes of isolated prolonged PT*****

A

Think extrinsic pathway - TF and F7, F7a activate F10, F10a activate thrombin

Factor deficiency or inhibition
- Warfarin (factor II, VII, IX, X)
- Liver disease (↓synthesis)
- Inherited factor VII deficiency (rare)

Vitamin K:
- Causes of cholestasis (↓vitamin K absorption)
- Vitamin K deficiency (factor II, VII, IX, X)

48
Q

Causes of isolated prolonged aPTT

A

Think about intrinsic pathway - aPTT measure F8 and F9 activity, activate F10a/F5a cascade in amplification phase

Factor inhibition:
- Heparin contamination (most common in in-pt)
- Lupus anticoagulant (a/w thrombosis)
- Acquired haemophilia A (rare, due to F8 inhibitor)
Factor deficiency:
- Congenital haemophilia A/B (usually in men)
- Von Willebrand disease
- Factor XII deficiency (10% normal population, NOT a/w bleeding)

49
Q

Causes of prolonged PT and aPTT *****

A

F7,8,9 across intrinsic and extrinsic pathway:

Consumption:
- Diffuse intravascular coagulation (DIC)
Production/inhibition:
- Warfarin and Vitamin K deficiency (factor II, VII, IX, X)
- Liver disease (↓synthesis) and cholestasis
- Factor X and fibrinogen deficiency (rare)

50
Q

Causes of bleeding with normal clotting times

A

Platelet disorders*

Mild von Willebrand disease
Mild coagulation factor deficiency
Factor XIII deficiency (just for fibrin cross-linking

51
Q

Approach to isolated prolonged PT

A

□ Repeat and confirm
□ Look for features of cholestasis and LIVER DISEASE*** and their causes
□ Hx of WARFARIN use

Isolated PT Treatment:
□ Parenteral vitamin K
□ VitK + FFP + PCC if warfarin overdose

52
Q

Approach to isolated prolonged aPTT

A

□ Repeat and confirm

□ Most commonly HEPARIN and LUPUS COAGULANT
→ perform mixing test to r/o

□ Check HEMOPHILIA A/B in men (XLR) and vWD in both genders (AD)
→ perform specific factor assay and vWF assay

□ Management:
→ FACTOR CONCENTRATES for haemophilia A/B
→ DDAVP for mild haemophilia and vWD

53
Q

Approach to concurrent prolonged PT + aPTT

A

□ Repeat and confirm

□ Consider DIC
→ Measure fibrinogen, D-dimer, platelet + look for underlying cause
→ Classical result: ↑PT, ↑aPTT, ↓fibrinogen, ↓platelet + fragmented RBCs

□ Management:
→ FFP to replenish consumed coagulation factors in active bleeding
→ Treat underlying cause only if no bleeding (prophylactic FFP may ↑risk of thrombosis)

54
Q

Haemophilia A, B, C and acquired factor deficiencies

Define underlying factor deficiencies and inheritance patterns

A

□ Haemophilia A due to inherited deficiency of factor VIII (XLR)
□ Haemophilia B (Christmas disease) due to inherited deficiency of factor IX (XLR)
□ Haemophilia C (Rosenthal syndrome due to inherited deficiency of factor XI (AR)

□ Acquired factor deficiencies due to autoAb vs clotting factors (most commonly VIII)

55
Q

acquired factor deficiency

  • Patient demographic
  • Typical presentation
A

Postpartum
Autoimmune diseases
Old and poorly mobilized

Classical presentation is retroperitoneal haematoma due to poor mobilization
presents with back pain + profound anaemia

56
Q

Clinical presentation of haemophilia

Age of diagnosis for mild, moderate and severe haemophilia

A

Age of diagnosis: average 1mo, 8mo and 36mo for severe, moderate, mild haemophilia

Presentations:
1. Neonatal Cephalhaematoma and ICH

  1. Haemarthrosis (80%) at weiight-bearing joints: stiffness, pain, swelling
  2. Soft tissue haematoma:
    - Muscle haematoma, commonly in calf and psoas muscles: Lead to compartment syndrome (acute bleed into calf) and Femoral nerve compression in psoas bleed
    - Acute abdomen
    - Haemophilic pseudotumor in pelvis/ bone
  3. Mucosal bleed:
    - Oropharyngeal, GI bleed, bowel wall haematoma
    - Haematuria
57
Q

Complications of severe haemophilia

A

Haemophilic arthropathy and joint deformation
Bloodborne infections, eg. HIV, HBV, HCV
Inhibitor development: develop alloAb vs exogenous factor/ treatment resistance

58
Q

Typical lab tests for suspected haemophilia

A

□ Prenatal diagnosis: often presumed based on sex on USG (XLR)

□ Clotting profile: isolated prolonged aPTT that is corrected in mixing studies

□ Specific factor assay: ↓activity (<40%) in factor VIII (haemophilia A), IX (haemophilia B)

□ Genetic testing: appropriate → identify the mutation that can be used for relative screening

59
Q

Management of Haemophilia

A

General measures:

  • Avoid invasive procedures
  • Dental hygiene
  • Exercise
  • Avoid antiplatelet/ anticoagulants

DDAVP for mild haemophilia A
- MoA: promote release of factor VII and vWF (F8 carrier) from storage pools in platelet granules and endothelial cells

Recombinant factor replacement

Specific complications:
Haemarthrosis: analgesics (eg. COX-2, Panadol → avoid NSAID), RICE as needed
Muscle haematoma: surgical decompression
Haematuria: forced diuresis
Mucosal bleeding: add antifibrinolytic agents, eg. tranexamic acid, aminocaproic acid

60
Q

Von Willebrand Disease

Major Types and definition

A
61
Q

Von Willebrand disease

Physiological function of vWF
Pathogenesis of vWD

A

Pathogenesis: due to qualitative or quantitative defect in von Willebrand factor (vWF)

Physiology: a large multimeric glycoprotein secreted by endothelium as ultra-large multimers → eventually cleaved by ADAMTS13 into smaller polymers (less active) → degraded by other proteases in plasma

Main functions:
→ Carrier protein for factor VIII → prevent rapid degradation in plasma
→ Mediates platelet adhesion from GPIb to collagen in sub-endothelial matrix

Pathology: genetic defect in VWF gene (ch12) → defective platelet adhesion + ↓factor VIII level

62
Q

Clinical features of vWD

A

vWF affects both platelet adhesion to collagen AND factor 8 function:

Mucocutaneous bleeding (deep-seated bleeding in Type 3 vWD only)
Deep-seated bleeding/ Joint and tissue bleeding: usually only seen in types 2N and 3

Heavy menstrual bleed (60-90%) in women

Post-partum bleeding (62%) in women

63
Q

Typical investigations and results in vWD

Screening assays

A

Basics: isolated ↑aPTT ± thrombocytopenia in type 2B

vWD screening assays:

  1. vWF antigen (vWF:Ag) titre
  2. vWF activity (vWF:Act): measures binding activity of vWF
    - Ristocetin cofactor assay (vWF:RiCof)
    - Collagen binding assay
    - Factor VIII activity

vWF Act:Ag ratio

Multimer analysis

Ristocetin-induced platelet aggregation (RIPA)

64
Q

Management of vWD

A

Trial of DDAVP (in all non-type 3 patients)

vWF concentrates in major bleeding/surgery; refractory to DDAVP

Antifibrinolytic agents: alone or with DDAVP/vWF in mucosal bleeds

65
Q

Approach to low platelet

A

Repeat and confirm:Citrate blood

Thrombocytopenia with Pancytopenia:BM exam for failure/ suppression

Isolated thrombocytopenia:Liver disease, ITP, DRUG

Assess bleeding risk: Bleeding history + P/E + Clotting profile + Fundoscopy

66
Q

Compare between platelet disorder and coagulation disorders:

Presence of subcutaneous bleed, mucosal bleed, intracranial bleed, retinal bleed and intra-muscular bleed

A

Specific to Platelet: Petechiae, purpura, mucosal and retinal bleed

Specific to Coagulation: Intramuscular bleed and intra-articular bleed

Both: Ecchymosis, Intracranial bleed

MBBS VI - SpC - Medicine (80 decks)

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