Coagulation in the lab and bleeding disorders

Question 1

APTT test
Activated partial thromboplastin time

Activates clotting via the _____ pathway, using glass etc.
Involves all factors except ____
Exclusive to APTT: ____, __, __, __
e.g a low factor _, ____ APTT

Venous blood sample with ____ (stops clotting), collect plasma, add ____ and ___, + ____ to overcome chelation and time

Answer 1

Activated partial thromboplastin time

Activates clotting via the instrinsic pathway, using glass etc.
Involves all factors except VII
Exclusive to APTT: XII, XI, IX VIII
e.g a low factor 8, prolonged APTT

Venous blood sample with citrate (stops clotting), collect plasma, add phospholipid and activator, + calcium to overcome chelation and time

Question 2

Prothrombin time PR

Activates ____ pathway, ____ need for factor _ and _ as soooo much ____ _____ present

Addition of ____ _____+ ____
Factors involved: __, _, _, ____, ____

PR is ratio (___ ____ over ___). Is close to 1

Answer 2

Activates extrinsic pathway, bypasses 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 3

Common pathway deficiency effects on APTT and PR

Answer 3

Will cause a degree of prolongation in both

Question 4

TCT

Answer 4

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

Used to give absolute fibrin number and affects of inhibitors.

Question 5

Mixing studies 1:1

Post test e.g APTT. So if ____ APTT
So if a subject has __-__% of normal ‘x’ clotting factor, test (APTT) will be completely ____. If ___ factor _____.
-If __% conc ____ plasma is added, if there is a _____ _____, it will ____.
-Sample will ___ fully correct in the presence of an _____

Thus if long APTT can differentiate

Answer 5

Post test e.g APTT. So long APTT
So if a subject has 40-50% of normal ‘x’ clotting factor, test (APTT) will be completely normal. If none prolonged.
-If 50% conc normal plasma is added, if there is a FACTOR deficiency, it will correct.
-Sample will NOT fully correct in the presence of an inhibitor

Thus if long APTT can differentiate

Question 6

Note about natural inhibitors and APTT

Answer 6

Antithrombin, protein C and protein do NOT affect APTT.

Question 7

Prolonged APTT and not corrected 1+1

Answer 7

-Lupus anticoagulant: May be a part of antiphospholipid syndrome (AI) which causes excess clotting. May be seen transiently in sick patients. Defining feature, NO BLEEDING
Interfere with phospholipid in the assay
- Factor inhibitors, very rare. AI antibodies against factors (often VIII, acquired haemophilia). Brusing etc so should be considered
-DRUGS: other cue card (heparin, dabigatran)

Question 8

How does heparin cause prolonged APTT and 1+1

what is heparin

Answer 8

Typically heparin upregulates antithrombin, so prolonged 1+1.
Typically used to lock a central line, so blood being drawn form here contaminated.
If protamine used, will correct?

Prolonged TCT?

Question 9

Dabigatran

Answer 9

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

Question 10

Test interpretation: 
APTT long, normal PR
PR long, normal APTT
Both high
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

In general other tests

Answer 11

Single factor assays, whole blood clotting tests, primary haemostasis (platelet function, aggregations, assay), D-dimers (broke down fibrin)

Question 12

Reasons for multiple factor deficiencies

Answer 12

• 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 13

Warfarin
Inhibits _____ of vitamin _, prevents ____ domain on these coagulation factors being ____.
Reversed by vitamin _
Used in ___, ____ and other thrombotic disorders

Answer 13

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 14

Haemophilia

Answer 14

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 15

Von Willebrand factor and low factor 8

VWF is the carrier of factor _ in the blood
Made in ______.
Disease with a lack of ____ is ___ _____disease. Is ____ _____ and most _____ hereditary bleeding disorder

Presentswith ____ _____APTT, low __, low ___, abnormal _____ screen.

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

Answer 15

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

Question 16

Note on factor 12 deficiency

Answer 16

Prolonged APTT WITH NO BLEEDING HISTORY, as is not physiological