Blood Disorders

Question 1

Thrombocytopaenia

Answer 1

Low platelets
Can be due to reduced platelet production, increased platelet destruction or sequestration of platelets (splenic pooling)

Question 2

Aggregometry

Answer 2

Diagnostic test of choice for platelet function defects
Involves using a spectrophotometer to test light impedence of platelets in plasma. If the absorbance value is low, i.e., no light impedance, platelets have clotted. If the absorbance value is high, i.e., light impedance, platelets have not clotted. Agents are added in order to test clotting, e.g., collagen, thrombin, adrenaline.

Question 3

APTT

Answer 3

Activated partial thromboplastin time
Activator added to platelet-poor plasma in the presence of Ca+2 and phopholipids to trigger XII —> XIIa
Normal: 24-37 seconds
Measures all factors except factor VII, most sensitive to XII and XI
Commonly prolonged in haemophilia (reduced VIII and IX)

Question 4

What does a prolonged APTT indicate?

Answer 4

That there is a deficiency of a factor in the intrinsic or common pathway or that there is an inhibitor present. Next step is to attempt to correct the APTT

Question 5

Isolated VII deficiency test results

Answer 5

Normal APTT but very prolonged prothrombin time

Question 6

If APTT does not correct, what is indicated?

Answer 6

That there is an inhibitor present rather than a factor deficiency

Question 7

Clotting inhibitors

Answer 7

Lupus anticoagulant
Acquired factor inhibitors
Unfractioned heparin
Dabigatran (oral thrombin inhibitor)

Question 8

Prothrombin ratio

Answer 8

Prothrombin time of patient/Prothrombin time of normal pooled control
Normal = 0.8-1.2
Add TF to platelet-poor plasma in the presence of calcium and measure clotting time (around 12-15 seconds)
Used to monitor warfarin therapy

Question 9

What does the prothrombin ratio detect?

Answer 9

Defects in II, VII and X (three of the four vitamin K dependent factors)

Question 10

INR

Answer 10

International normalised ratio
Corrected PR used for warfarin monitoring. Necessary because clotting time and therefore PR can be variable depending on source of thromboplastin.

Question 11

Thrombin clotting time

Answer 11

Add thrombin to platelet-poor plasma and measure clotting time (dependent on thrombin concentration used)
Sensitive to heparin, dabigatran, fibrin degradation products and fibrinogen abnormalities

Question 12

Lupus anticoagulant

Answer 12

Antibodies in plasma that bind phospholipid
Prolongs APTT and 1+1 but doesn’t interfere with physiological clotting
These people don’t bleed

Question 13

Antiphospholipid syndrome

Answer 13

Antibody binds endothelium causing excess clotting

Question 14

Haemophilia A

Answer 14

X-linked condition
Factor VIII
Treated by factor VIII replacement, given prophylactically in children to prevent joint damage

Question 15

Haemophilia B

Answer 15

X-linked condition
Factor IX
Treated by factor IX replacement, given prophylactically in children to prevent joint damage

Question 16

Von Willebrand’s disease

Answer 16

Autosomal dominant (type 1 + 2) or recessive (type 3)
Defect of primary haemostasis resulting from reduced VWF
Patients won’t get proper platelet plugs
Because factor VIII circulates bound to VWF, VIII may also be reduced and give coagulation effects

Question 17

Why do some antibiotics interact with warfarin?

Answer 17

Some antibiotics disrupt the microbiota of the gastrointestinal tract which can reduce fat and soluble vitamin absorption, therefore vitamin K absorption is reduced and patients can become deficient. Since vitamin K is a wafarin antagonist, the effects of warfarin in these patients can be exacerbated and should be monitored.

Question 18

Fibrinolysis

Answer 18

Breakdown of fibrin
Labs can measure the level of D-dimer in the blood, which are cross-linked fragments of fibrin and imply clot degradation
High levels of D-dimer found in venous thrombosis and DIC (sensitive but not specific)

Question 19

Virchow’s triad

Answer 19

Stasis of blood flow
Hypercoagulability
Changes to the blood vessel wall

Question 20

Causes of VTE

Answer 20

Surgery/trauma
Immobility
Hospitalisation
Malignancy
HRT/OCP/pregnancy

Question 21

Thrombophilia

Answer 21

Higher propensity to clot

Testing for inherited thrombophilia mainly focused on younger patients with spontaneous, unexplained VTE

Question 22

Most common abnormality associated with familial thrombosis

Answer 22

Activated protein C resistance secondary to a point mutation in the factor V gene

Question 23

How does the OCP affect the likelihood of thrombosis?

Answer 23

OCP increases the likelihood of thrombosis due to interaction with factor V Leiden, which is a variant form of factor V and increases DVT risk

Question 24

Factor V Leiden

Answer 24

In normal coagulation, factor Va is inactivated by protein C by cleaving the factor V molecule at an Arg residue. Factor V Leiden is a mutated version of factor V which has a Glu residue instead of the Arg residue and is therefore resistant to cleavage and therefore protein C is unable to act as an anticoagulant.

Question 25

Prothrombin 20210 mutation

Answer 25

Second most common genetic thrombophilic abnormality

Mutation in the promoter region of the prothrombin gene leading to excess production of prothrombin

Question 26

Signs and symptoms of DVT

Answer 26

Unilateral leg pain
Swelling
Discolouration
Oedema

Question 27

Signs and symptoms of PE

Answer 27

Shortness of breath
Chest pain
Tachycardia
Tachypneoa
Hypoxia

Question 28

VTE diagnosis

Answer 28

Well’s score for DVT
High risk patients should be referred for radiology to exclude or confirm thrombus (ultrasound for DVT, CTPA for PE)
D-dimer test

Question 29

Well’s score

Answer 29

More than 2 points = likely DVT, less than 2 points = unlikely DVT
1 point awarded for various criteria, including but not limited to malignancy, leg swelling, tenderness, pitting oedema, previous DVT

Question 30

Heparins

Answer 30

Often used while waiting for the full effect of warfarin
Most often subcutaneous LMWH used because of its good bioavailability – in NZ, called enoxaparin
Accelerate inhibition of activated thrombin and Xa in plasma

Question 31

Rivaroxaban

Answer 31

Binds and inhibits Xa

Question 32

Dabigatran antidote

Answer 32

Idarucizumab

Question 33

Rivaroxaban antidote

Answer 33

Xa decoy molecule

Question 34

Classic triad of PE

Answer 34

Pleuritic pain
SOB
Haemoptysis

Question 35

Febrile neutropenia

Answer 35

Potentially catastrophic complication of treatment of leukaemia and other cancers
Development of fever in a patient with abnormally low neutrophil granulocytes in the blood

Question 36

Describe the blood tests that you would expect to see in febrile neutropenia

Answer 36

Total WBC count could be fine or low
Blasts will generally be high
Neutrophils will be very low
Lymphocytes could be low or normal
Platelets will be very low
Haemoglobin likely to be slightly low

Question 37

Tazocin

Answer 37

Piperacillin and tazobactam
Very broad spectrum antibiotic
Bactericidal against pretty much everything – almost all aerobic bacteria

Question 38

Gentamicin

Answer 38

Active against almost all aerobic gram -ve bacilli

Question 39

Do patients with severe neutropenia benefit from being nursed in isolation?

Answer 39

Studies show isolation reduces the number of days of fever but has no significant impact on overall mortality