Thrombotic Disorders

Question 1

thrombocytopenia

Answer 1

describes a low platelet count

Question 2

normal platelet count

Answer 2

150 to 450 x 10^9/L

Question 3

thrombocytopenia aetiology

Answer 3

p latelet disorders: ITP, TTP, DIC
l eukaemia
a plastic anaemia
t rauma
e thanol
l iver disease
e enlarged spleen
t oxins/ drugs: HIT
s epsis

Question 4

drugs that can induce thrombocyopenia?

Answer 4

quinine
diuretics
sulphonamides
aspirin
thiazides

Question 5

viral infections that can induce thrombocytopenia?

Answer 5

EBV
HIV
hepatitis

Question 6

immune (idiopathic) thrombocytopenic purpura (ITP)

Answer 6

an immune-mediated reduction in the platelet count.

antibodies directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.

Question 7

ITP adults vs children

Answer 7

adults: chronic

children: acute; follows an infection or vaccination

Question 8

ITP in children has a high mortality

Answer 8

false

usually runs a self-limiting course over 1-2 weeks

Question 9

ITP epidemiology

Answer 9

more common in older females

Question 10

ITP presentation

Answer 10

asymptomatic: detected incidentally following routine bloods

symptomatic
- petichae
- purpura
- bleeding (epistaxis)

Question 11

ITP management

Answer 11

1. oral prednisolone
2. pooled normal human immunoglobulin (IVIG)
3. splenectomy (uncommon)

Question 12

evan’s syndrome

Answer 12

ITP in association with autoimmune haemolytic anaemia (AIHA)

Question 13

thrombotic thrombocytopenic purpura (TTP) pathophysiology

Answer 13

abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels

Question 14

what underlying enzyme is deficient in TTP?

Answer 14

deficiency of ADAMTS13

ADAMTS13 is a metalloprotease enzyme which breaks usually down (‘cleaves’) large multimers of von Willebrand’s factor

Question 15

TTP overlaps with what

Answer 15

haemolytic uraemic syndrome (HUS)

Question 16

TTP epidemiology

Answer 16

rare

typically adult females

Question 17

TTP presentation

Answer 17

• f ever
• a ltered mental state: due to microemboli
• t hrombocytopenia
• h aemolytic anaemia
• r enal failure

remember father

Question 18

TTP triggers

Answer 18

idiopathic

congenital

infections: HIV

pregnancy

drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir

pancreatitis

remember: ici pdp

Question 19

gestational thrombocytopenia

Answer 19

relatively common

results from a combination of dilution, decreased production and increased destruction of platelets

Question 20

why would you have an increase destruction of platelets in pregnancy?

Answer 20

increased work of the maternal spleen leading to mild sequestration

Question 21

typical course of ITP

Answer 21

a chronic relapsing course

Question 22

differentiating between ITP and gestational thrombocytopenia often relies on what?

Answer 22

a careful history

Question 23

gestational thrombocytopenia may be considered more likely vs ITP if?

Answer 23

platelet count continues to fall as pregnancy progresses

but this is not a reliable sign

Question 24

if the patient becomes dangerously thrombocytopenic in gestational thrombocytopenia then how do you treat it?

Answer 24

steroids and a diagnosis of ITP assumed

Question 25

what would you do with a woman who is found to have low platelets during a booking visit or those with a previous diagnosis of ITP?

Answer 25

tested for serum antiplatelet antibodies for confirmation.

Question 26

why is it important to differentiate between ITP and gestational thrombocytopenia

Answer 26

gestational thrombocytopenia doesn’t affect the neonate

BUT ITP can do if maternal antibodies cross the placenta

Question 27

how do you approach the thrombocytopenic neonate?

Answer 27

platelet transfusion: depends on degree of thrombocytopenia

serial platelet counts: to check for inherited thrombocytopenia.

Question 28

drug-induced thrombocytopenia is probably immune-mediated

Answer 28

true

Question 29

medications that can cause drug-induced thrombocytopenia

Answer 29

quinine
diuretics: furosemide
antibiotics: penicillins, sulphonamides, rifampicin
NSAIDs
anticonvulsants: carbamazepine, valproate
heparin
abciximab

Question 30

when should you offer platelet transfusions?

Answer 30

<30 x 10 ^9 with clinically significant bleeding

Question 31

which WHO bleeding grade patients should be offered platelet transfusions?

Answer 31

grade 2

(haematemesis, melaena, prolonged epistaxis)

Question 32

in severe bleeding, what is the MAXIMUM platelet count in which transfusion can be offered?

and what WHO bleeding grade would this be?

Answer 32

<100 x 10 ^9 with severe bleeding

bleeding grades 3 & 4 or at critical sites (CNS)

Question 33

patients with bleeding at critical sites, such as the CNS should be offered platelet transfusion if their count is<30 x 10 9

Answer 33

platelet thresholds for transfusion are higher (< 100 x 10^ 9) for patients with severe bleeding

Question 34

Which transfusion type has the highest risk of bacterial contamination?

Answer 34

Platelet transfusion.

Question 35

what levels of platelet should be aimed for a platelet transfusion

(due to thrombocytopenia before surgery/ invasive procedure)

Answer 35

> 50×10^9/L: most patients

50-75×10^9/L: high risk of bleeding

100×10^9/L: surgery at critical site

Question 36

If no active bleeding or planned invasive procedure what is the platelet threshold for plt transfusion?

Answer 36

10 x 109

except where platelet transfusion is contradindicated or there are alternative treatments for their condition

Question 37

Which conditions would you usually not perform transfusion for and why

Answer 37

chronic bone marrow failure

autoimmune thrombocytopenia

heparin-induced thrombocytopenia (HIT)

thrombotic thrombocytopenic purpura (TTP)

platelet transfusion is contradindicated or there are alternative treatments for their condition

Question 38

Under homeostatic conditions, coagulation and fibrinolysis are coupled

Answer 38

true

Question 39

activation of the coagulation cascade yields what that converts what to what

Answer 39

thrombin
fibrinogen
fibrin

Question 40

final product of hemostasis

Answer 40

stable fibrin clot

Question 41

what does the fibrinolytic system do

Answer 41

breaks down fibrinogen and fibrin.

activation of the fibrinolytic system generates plasmin (in the presence of thrombin) which is responsible for the lysis of fibrin clots.

the breakdown of fibrinogen and fibrin results in polypeptides (fibrin degradation products)

Question 42

What is a key factor to the function of the fibrinolytic system

Answer 42

plasmin in the presence of thrombin

plasmin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for fibrinolysis.

Question 43

What is the pathophysiology of Disseminated intravascular coagulation?

Answer 43

In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding.

Question 44

Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions.

Answer 44

true

Question 45

One critical mediator of DIC is the release of what?

Answer 45

transmembrane glycoprotein (tissue factor =TF).

Question 46

Why does DIC readily develops in patients with extensive trauma?

Answer 46

TF present on the surface of many cell types (including endothelial cells, macrophages, and monocytes)

TF is also abundant in tissues of the lungs, brain, and placenta

Sets off coagulation cascade

Question 47

TF is released in response to exposure to?

Answer 47

cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin.
This plays a major role in the development of DIC in septic conditions

Question 48

TF is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage

Answer 48

true

Question 49

Which factors are associated with extrinsic pathway?

Answer 49

Factor VII

Question 50

Which factors are associated with intrinsic pathway?

Answer 50

I, II, IX, X, XI, and XII

Question 51

Describe how TF sets off the coagulation cascade?

Answer 51

Upon activation, TF binds with coagulation factors

that then triggers the extrinsic pathway (via Factor VII)

which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation.

Question 52

What are some causes of DIC?

Answer 52

sepsis
trauma
obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
malignancy

Question 53

What is the typical blood pictureof DIC?

Answer 53

low platelets
prolonged APTT, prothrombin and bleeding time
fibrin degradation products are often raised

Question 54

What might you see in the blood films for DIC?

Answer 54

schistocytes due to microangiopathic haemolytic anaemia

Question 55

What is Factor V Leiden?

Answer 55

activated protein C resistance

Question 56

What is the most common INHERITED thrombophilia

Answer 56

Factor V Leiden

Question 57

Pathophysiology of FVL?

Answer 57

It is due to a gain of function mutation in the Factor V Leiden protein. The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal. This explains the alternative name for factor V Leiden of activated protein C resistance,

Question 58

Describe pathophysiology of FVL in terms of heterozygotes and homozygotes

Answer 58

Heterozygotes have a 4-5 fold risk of venous thrombosis. Homozygotes have a 10 fold risk of venous thrombosis but the prevalence is much lower at 0.05%.

Question 59

Screening for factor V Leiden is recommended

Answer 59

false
ot recommended, even after a venous thromboembolism. The logic behind this is that a previous thromboembolism itself is a risk factor for further events and this should dictate specific management in the future, rather than the particular thrombophilia identified.