Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MD2 Haematology > Bleeding Disorders and Coagulopathies > Flashcards

Bleeding Disorders and Coagulopathies Flashcards

1
Q

Define haemostasis

A

Physiological process of stopping or arresting bleeding or keeping the blood within the damaged vasculature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define thrombosis

A

Pathological process causing disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the 3 key steps in haemostasis?

A

Initial response: vasoconstrction, endothelial activation

Platelet plug formation

Fibrin clot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe the coagulation pathway

A

Sequential activation of clotting proteins (serine proteases; activated by proteolytic cleavage), enhanced by co-factors V and VIII, ultimately leading to formation of fibro

Essential components: phospholipids, calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the significance of AT deficiency?

A

Strong risk factor for thrombosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is antithrombin?

A

Serine protease inhibitor (inhibits factors 9-12 and thrombin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is TFPI and what does it do?

A

Tissue factor pathway inhibitor

Inactivates Xa in the presence of VII and TF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What do deficiencies in the fibrinolytic pathway predispose to?

A

Thrombosis (increase risk 2x)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the initiation phase of coagulation

A

Physiological clotting is initiated by exposure of TF due to vascular damage (aggregated platelets display integrin receptors and phospholipid surface markers which concentrates clotting factors)

TF interacts with VII/VIIa and activates fX to fXa

fXa then generates small amount of thrombin; this is not adequate to sustain haemostasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 3 phases of the “new coagulation model”?

A

Initiation

Propagation

Stabilisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the propagation phase of coagulation

A

Initial thrombin burst then activates XI to XIa and also generates Va and VIIIa (TF/VIIa can also generate IXa)

Activated platelets release fV

Thrombin and XIa set up a feedbook loop that generates even more thrombin that sustains propagation of coagulation

XII has no role in this cascade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What occurs in the stabilisation phase of cogulation?

A

Thrombin stimulates fibrin and XIIIa formation, which produces a cross-linked fibrin clot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the pathological process underlying DIC?

A

Systemic dysregulated clotting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What 3 processes enable undamaged endothelium to resist clotting, controlling the extent of clot formation by limiting it to the regions of endothelial damage?

A

Thrombomodulin (expressed on endothelial cell surface) binds thrombin to generate activated protein C, which inactivates Va and VIIIa

Soluble antithrombin inactivates thrombin and Xa

Thrombin activates fibrinolysis to modify clot size

NB All these processes occur simultaneously

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What screening tests are performed to look for haemostatic defects?

A

Platelet count

APTT

PT

Thrombin time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the normal platelet count?

A

150-400

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is APTT and what is the normal reference range?

A

Activated Partial Thromboplastin Time

24-32 secs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is PT and what is the normal reference range?

A

Prothrombin time

10-12 secs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the normal reference range for thrombin time?

A

14-22 secs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What physiological factors influence APTT?

A

Surface activating agents (ellagic acid, kaolin)

Phospholipid

Calcium

Thrombin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What physiological factors influence PT?

A

Thromboplastin

Tissue factor

Phospholipid

Calcium

Thrombin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What haematological tests are used to measure the intrinsic vs the extrinsic pathway?

A

Intrinsic: APTT

Extrinsic: PT

Common pathway: TT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What physiological factors influence the thrombin time

A

Thrombin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

List 6 common sample collection errors made when performing screening tests for haemostatic defects

A

Partially filling tubes

Incorrect tube

Vacuum leak and citrate evaporation

Clot in tube

Underfilling

Heparin contamination (blood drawn from IV lines)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What biological effects may cause error in screening for haemostatic defects?

A

Haematocrit >55 or <15

Lipaemia

Hyperbilirubinaemia

Haemolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What laboratory errors may influence the results of screening for a haemostatic defect?

A

Delay in testing

Prolonged incubation at 37 degrees C

Freeze/thaw deterioration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What correction studies should be performed following an abnormal APTT/PT test result, to ensure this is a true result?

A

Mix 1/2 patient’s sample and 1/2 control (pooled plasma from normal individuals) and re-perform the APTT or PT

If the patient has a factor deficiency, the APTT/PT will normalise (due to presence of factors from normal sample)

If an “ïnhibitor” is present (e.g. lupus anticoagulant), there will be a persistent abnormality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

If a prolonged APTT but normal PT result is obtained for a patient, and the APTT is corrected with a mixing study, what is the DDx?

A

Factor deficiency (VIII, IX, XI, XII)

Early DIC

Heparin Rx (correction is variable)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

If an abnormal APTT but normal PT result is obtained for a patient, and the abnormality persists with a mixing study, what is the DDx?

A

Lupus anticoagulant (common)

Inhibitors towards specific coagulant factors VIII, IX, XI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

If a normal APTT but prolonged PT result is obtained for a patient, and the PT is corrected with a mixing study, what is the DDx?

A

Factor deficiency (VII; rare)

Liver disease (common)

Vitamin K deficiency (common)

Warfarin (common)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

If a normal APTT but prolonged PT result is obtained for a patient, and the abnormality persists with a mixing study, what is the DDx?

A

Antiphospholipid Abs (uncommon)

Abs to VII (rare)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

If a prolonged APTT and PT result is obtained for a patient, and the APTT/PT are corrected with a mixing study, what is the DDx?

A

Isolated deficiency in common pathway: factors V, X, II and fibrinogen

Multiple factor deficiencies (common): liver disease, vit K deficiency, warfarin, DIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

If a prolonged APTT and PT result is obtained for a patient, and the abnormality persists with a mixing study, what is the DDx?

A

Inhibitors towards V, X, II, fibrinogen (rare)

Antiphospholipid Abs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Factors in the intrinsic pathway

A

XII

XI

IX

VIII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Factors in the extrinsic pathway

A

TF

VII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Factors in the common pathway

A

X

V

Thrombin

Fibrinogen

XIII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Causes of prolonged PT

A

Warfarin (indirectly inhibits factors II, VII, IX, X)

Liver disease

Vit K deficiency

DIC

Factor VII deficiency

38
Q

Causes of prolonged APTT

A

Heparin Rx

Liver disease

Lupus anticoagulant

DIC

von Willebrand’s disease

Haemophilia (factor VIII, IX deficiency)

Factor XII, XI deficiency

39
Q

Causes of prolonged TT

A

DIC (decreased fibrinogen)

Liver disease

Heparin

40
Q

List 7 common bleeding disorders

A

Von Willebrand disease

Haemophilias

Disorders of platelet numbers and function

DIC

CLD with cirrhosis

Renal failure

Use and toxicity of anti-platelet drugs, heparins, warfarin and newer oral anticoagulants

41
Q

What features on Hx are important to assess in a patient presenting with a possible bleeding disorder?

A

Age at onset

Spontaneous or post-traumatic

Sites/frequency of bleeds

FHx

Medicinal therapy (anti-platelet Rx and anti-coagulants)

Therapy received and response

Any convincing evidence of “excessive bleeding”?

42
Q

Distinguish between purpuric and coagulation disorders in terms of presence/absence of petechiae and superficial echymoses, haematoma and haemarthrosis occurrence, frequency of late bleeding, gender and FHx

A
43
Q

What are the 4 most common hereditary bleeding disorders?

A

Haemophilia A or B

Von Willebrand disease

Factor deficiency

Platelet disorders (Glanzmanns thrombasthenia or Bernard Soulier)

44
Q

What is Glanzmanns thrombasthenia?

A

Platelets lack glycoprotein IIb/IIIa

As a result, no fibrinogen bridging of platelets to other platelets can occur, and bleeding time is significantly prolonged

45
Q

What is Bernard Soulier?

A

Deficiency of glycoprotein Ib, the receptor for von Willebrand factor

46
Q

List 5 common acquired bleeding disorders

A

Liver disease

Vitamin K deficiency

DIC

Excessive anticoagulation

ITP

47
Q

What signs may be seen in a patient with a bleeding disorder?

A

Petechiae (including palatal) and purpura

Gum bleeds

Large ecchymoses

Leg wasting and joint deformity from haemarthrosis

Telangiectasia

48
Q

What is senile purpura?

A

Common, benign condition seen in the elderly and characterised by recurrent formation of large purple ecchymoses on the extensor surfaces of the forearms following minor trauma

Due to atrophy of dermal tissue and fragility of blood vessels

49
Q

What is Von Willebrand disease?

A

Commonest bleeding disorder!

Heterogeneous haemorrhagic disorder caused by deficiency or dysfunction of von Willebrand factor (may be inherited or acquired)

50
Q

Where is von Willebrand factor synthesised?

A

Megakaryocytes and endothelial cells (undergoes dimerisation in the ER and multimerisation in the Golgi apparatus)

51
Q

What are the functions of vWF?

A

vWF mediates platelet adhesion at site of injury and stablises FVIII in the circulation

Wherever platelet aggregation is needed, coagulation is also necessary; vWF is like a “taxi” that carries FVIII to the proximity of a developing clot

52
Q

How does blood group influence levels of vWF? How does this influence presentation with type I von Willebrand disease?

A

Blood group contributes to ~25% variation in vWF level

ABO glycosylation of vWF influences clearance; people with non-O blood group have higher levels than those with O-group (AB has the highest)

ABO group therefore also modifies the penetrance of type I von Willebrand disease

53
Q

How is hereditary von Willebrand disease inherited?

A

Varies; there are AD and AR presentations (type I is AD)

54
Q

What is type I von Willebrand disease and how common is it when compared with other types of von Willebrand disease?

A

Partial quantitative deficiency of vWF; mild presentation (depending on blood group) with many cases going undiagnosed

70-80% of cases of von Willebrand

55
Q

What is type II von Willebrand disease?

A

Qualitative deficiency of vWF, resulting in mild to moderate bleeding

Many subtypes, with differences in vWF multimers (including presence of abnormal multimers in some subtypes)

56
Q

What is type III von Willebrand disease?

A

Virtually complete deficiency of vWF

57
Q

Describe 4 subtypes of von Willebrand disease type II

A

2A: decreased affinity of vWF for platelet due to decrease in multimers

2B: increased affinity of vWF for platelet due to vWF mutation (causes thrombocytopaenia)

2M: decreased platelet binding due to vWF mutation

2N: defective factor VIII binding site, so decreased FVIII level (DDx would include mild haemophilia)

58
Q

What screening tests can be performed to assess for von Willebrand disease and what results would be expected?

A

Bleeding time: prolonged

Platelet count: low in type 2B or pseudo-vWD

APTT: prolonged but variably (especially prolonged in type 2N, 3)

PFA (platelet function analyser): prolonged

59
Q

What specific tests can be performed for vWD?

A

vWAg: low (diagnostic if <0.30 IU/mL)

FVIII clotting activity (VIII C): may be decreased but often in normal range

Functional assays (ristocetin co-factor activity/collagen-binding assay): low

60
Q

Ix for vWD

A

Haemostatic screening tests

Specific vWF tests

Multimer analysis

61
Q

Mx of vWD

A

Desmopression (DDAVP)

Replacement therapy: FVIII/vWFAg concentrate, recombinant vWFAg concentrate, cryoprecipitate/FFP/platelets

Antifibrinolytics (e.g. transexamic acid)

Fibrin glue/fibrillar collagen preparation

62
Q

When should an acquired vWD be considered?

A

Late onset bleeding diathesis in a patient with a negative FHx; clinical manifestations are similar to type 1 and type 2 vWD (mild to moderate bleeding)

63
Q

What factors may predispose to vWD?

A

AI disease

Lymphoproliferative/myeloproliferative disorders (thrombocythaemia)

Monoclonal gammopathy

Drugs (e.g. ciprofloxacin, valproic acid)

Infectious disease

Valvular heart disease (esp AS; large multimers of vWF are destroyed by mechanical stress)

64
Q

What is the cause of pseudo-vWD?

A

Mutation in platelet integrin GpIb so that it has increased binding with vWF

65
Q

Describe the pathophysiology of haemophilia A

A

Factor VIII deficiency (which normally circulates bound to vWF, protecting it from proteolysis)

66
Q

How is haemophilia A inherited?

A

XR (males present with features of disease)

67
Q

How do levels of F VIII and IX correspond with the clinical presentation?

A

<1 U/dL: severe, spontaneous bleeding

1-5 U/dL: moderate bleeding with minimal trauma or surgery

5-30 U/dL: mild bleeding with trauma or surgery

68
Q

Is it more common to have severe spontaneous bleeding in haemophilia A or B?

A

A

69
Q

What is the typical clinical picture in haemophilia?

A

Most common presentation is severe spontaneous bleeding (70% in haemophilia A, 50% in haemophilia B)

70
Q

List 5 common clinical presentations of haemophilia A

A

Haemarthrosis

Subcutaneous and intramuscular haematomas

Psoas and retroperitoneal haematomas

Traumatic bleeding (bleeding from razor nicks uncommon, but delayed bleeding is common esp in tooth extractions, tonsillectomy, etc)

Slow wound healing

71
Q

What is the prognosis of haemophilia A?

A

Depends on severity

Nearly normal life span with factor VIII replacement

72
Q

Ix and expected results for haemophilia A

A

APTT: prolonged

INR: normal

Specific F VIII C assay: low

73
Q

DDx for haemophilia A

A

Haemophilia B

vWD (esp type 2N)

74
Q

Mx of haemophilia A

A

Purified or recombinant F VIII therapy

Transexamic acid

Topical thrombin

FFP (no longer therapy of choice)

75
Q

What difficulties are encountered in the Mx of haemophilia A?

A

Patients can develop inhibitors to factor replacement therapy; these can be overcome by the use of “bypassing agents” (which usually consist of variable amounts of activated and precursor vit K-dependent clotting factors which generate thrombin by bypassing the coagulation cascade)

Risk of HIV, HCV etc

76
Q

What is haemophilia B? Is it more or less common than haemophilia A? How is it inherited?

A

Factor IX deficiency

4-8x less common than haemophilia A

XR (and unlike haemophilia A, the spontaneous mutation rate is low so most patients have a FHx)

77
Q

How does severe disease manifest in haemophilia B compared with haemophilia A?

A

Identically

78
Q

Ix and results for haemophilia B

A

APTT: prolonged (although not sensitive to mild deficiency i.e. F IX 20-30%)

INR: normal

79
Q

Mx of haemophilia B

A

Prothrombin complex

Purified or recombinant F IX

80
Q

Why is Rx Hx and FHx so important to ask about in a patient with a suspected platelet disorder?

A

Rx: may be on antiplatelet or anticoagulant drugs, important to rule out drug causes when considering a Dx of ITP (ITP is a Dx of exclusion)

FHx: will identify inherited platelet receptor abnormalities

81
Q

What medications may cause thrombocytopaenia?

A

Heparin

Alcohol

Quinine/quinidine

Sulfa drugs

82
Q

What are some causes of thrombocytopaenia as a result of increased platelet destruction?

A

AI: ITP, SLE, drugs

Allo-immune: post-transfusion purpura, neonatal allo-immune thrombocytopaenia

Non-immune: hypersplenism, DIC/TTP/HUS

83
Q

What are 5 causes of thrombocytopaenia as a result of decreased platelet production?

A

Aplastic anaemia

Myelodysplasia

Leukaemic infiltration

Lymphoma infiltration

Fibrosis

84
Q

At what platelet count is there a risk of spontaneous bleeding?

A

<10-20 x10^9/L

85
Q

At what platelet count is there considered to be no significant increased risk of post-surgical bleeding?

A

>50-60 x 10^9/L (provided normal platelet function)

86
Q

What are some possible sources of error if a low platelet count is returned on routine FBE?

A

Spurious reduction in automated platelet count due to platelets clumping because of EDTA in collection tube, or blood clotting

87
Q

What types/sites of bleeding are often observed in thrombocytopaenia?

A

Skin and mucous membranes: petechiae, ecchymoses, haemorrhagic vesicles, gingival bleeding, epistaxis

Menorrhagia

GI bleeding

Intracranial bleeding

88
Q

List 6 congenital causes of platelet dysfunction

A

Glanzmann thrombasthenia

Bernard Soulier syndrome

Storage pool deficiencies

Wiskott-Aldrich syndrome

Tar syndrome

Constitutional

89
Q

List 6 acquired causes of platelet dysfunction

A

Anti-platelet Rx

Uraemia

Extracorporeal circulation (e.g. haemodialysis)

Myeloproliferative disorders

Paraproteinaemia

Hypothermia

90
Q

How can platelet function be assessed?

A

Thromboelastography (TEG)

Platelet aggregation studies (ADP, collagen, adrenaline, ristocetin)

Platelet function analysis (PFA)

Skin bleeding time (no longer preferred due to technical issues of standardisation and expertise)

91
Q

What will standard haemostatic screening tests miss?

A

Mild vWD

Mild haemophilia

F XIII deficiency

Platelet function disorder (platelet count will be normal)

92
Q

What is cryoprecipitate?

A

Prepared by thawing FFP between 1-6 degrees C and recovering the precipitate

Contains most of F VIII, fibrinogen, F XIII, vWF and fibronectin from the FFP

MD2 Haematology (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions