Lecture 12: Coagulation in the lab and bleeding disorders

Question 1

What pathway of coagulation does the APPT go down and what clotting factors does it test for?

Answer 1

• Intrinsic factor

- tests for all factors except VII

Question 2

Describe the process of measuring APTT

Answer 2

1. Venous blood sample collected into tube with citrate
2. Spin sample down to collect plasma
3. Add phospholipid and an activator
4. Add Ca to overcome citrate
5. Measure length of time until clot formation

Question 3

Prothrombin time PR

Answer 3

Activates extrinsic pathway, by passes need for factor 8 and 9 as so much tissue factor present

Addition of tissue factor+ calcium
Factors involved: VII, X, V, prothrombin, fibrinogen

PR is ratio (patient time over normal). Is close to 1

Question 4

Common pathway deficiency effects on APTT and PR

Answer 4

Will cause a degree of prolongation in both

Question 5

TCT

Answer 5

Thrombin clotting time, focuses on the last part of clotting, so thrombin and its ability to convert fibrinogen to fibrin.

Done by Adding thrombin.

Used to give absolute fibrin number and affects of inhibitors.

Question 6

When are mixing studies done and what is there purpose?

Answer 6

• Done after abnormal clotting test e.g APPT
• They are used to test whether there is a deficiency of a clotting factor or if there is an inhibitor present (has to go back into NORMAL range)
• note patient blood mixed with normal blood in 1:1 ratio (insures all factors present)

Question 7

What are the 3 types of inhibitors of coagulation that affect APTT?

Answer 7

• Lupus anticoagulant: No bleeding, potentially antiphospholid syndrome
• Factor inhibitors
• Drugs (heparin, dabigatran)

Question 8

Heparin upregulates ___ and us commonly used to…

Answer 8

Anti-thrombin

Lock central lines

Question 9

Dabigatran

Answer 9

Inhibits thrombin, so prolonged 1+1
Prolonged TCT
protamine will not correct for dabigatran

Question 10

Test interpretation:

• APPT prolonged, PT normal
• PT prolonged, APPT normal
• Both PT and APPT prolonged
• TCT prolonged

Answer 10

• APTT prolonged, Normal PR: 8,9,11,12 intrinsic
• PR high, normal APTT: 7, mild deficiences of 2, 5, 10, 1 (normal APTT quirk of test)
• Both PR and APTT high: 2, 5, 10 and 1 common deficiencies, or multiple factors
• TCT prolonged: fibrinogen deficiency or heparin/ dabigatran

Question 11

Reasons for multiple factor deficiencies

Answer 11

• Warfarin or vitamin K deficiencies (2,7,9,10)
• Massive blood loss
• DIC: Widespread activation of coagulation, causing thrombosis, followed by bleeding as clotting factors and platelets used up. Often low fibrinogen. (e.g meningococcal septicaemia)
• Liver disease: lack of production of factors, except VIII

Question 12

Warfarin

Answer 12

-Inhibits recycling of vitamin K, prevents GLA domain on these coagulation factors being carboxylated.
-Reversed by vitamin K
Used in AF, VTE and other thrombotic disorders

Question 13

Haemophilia

Answer 13

A: 8 most common, X-linked. Mild, moderate or severe
B:9, X-linked

Severe spontaneous bleeding into joints, or soft tissue bleeds causing tissue damage.
Intracranial bleeds. Can treat with the missing factor!

Question 14

Von Willebrand factor and low factor 8

Answer 14

VWF is the carrier of factor 8 in the blood
Made in megakaryocytes.
Disease with a lack of VWF in Von Willebrand disease. Is autosomal dominant and most common hereditary bleeding disorder

Presentswith moderately prolonged APTT, low f8, low VWF, abnormal platelet screen.

Symptoms, heavy menorrhagia, mucosal bleeding, autosomal history, bleeding