UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.

1. Hemostatic Work-up
Abdul-Kader Souid
Hemostasis = Platelet Plug (Primary Hemostasis)
+ Fibrin Clot (Secondary Hemostasis)
Collagen
Endothelial cell
Platelet recruitment Platelet plug Fibrin clot
Primary hemostasis Secondary hemostasis
+ADP
+Epinephrine
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2. Primary Hemostasis
2
Primary hemostasis work-up
• Platelet count
• Platelet function screen
• vWF antigen & activity
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Platelet Plug = Platelets + vWF
The three main functions of
von Willebrand factor (vWF)
3) Factor VIII delivery
1) Platelet adhesion to collagen
2) Platelet-platelet spreading and aggregation
Collagen
vWF
GPIb-a
Platelet
GPIIb/IIIa
vWF
Fibrinogen
Platelet
Factor VIII
Must know

3. Platelet Function Screen
The instrument measures the time taken for blood pulled through
a fine capillary to block a membrane coated with collagen-ADP
or collagen-epinephrine.
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Blood
Capillary tube
Coated membrane
Platelet Function Analyzer (PFA100)
Must know

4. Platelet Function Screen
• Normal vWF and platelet function = Collagen-epinephrine
<164 sec + collagen-ADP <116 sec
• Abnormal vWF (common) or abnormal platelet function (rare)
= Collagen-epinephrine >164 sec + collagen-ADP >116 sec
• Aspirin & NSAID (common) = Collagen-epinephrine
>164 sec + collagen-ADP <116 sec
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Blood
Capillary tube
Coated membrane
Must know

5. Secondary Hemostasis
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Work-up
PT/INR
aPTT
TT
Fibrinogen
TFPI = Tissue factor pathway inhibitor
prothrombin thrombin
(IIa)
fibrinogen
fibrin
prothrombinase complex
(X, V, PL, Ca2+
)
tissue factorVII
IX
XI
VIII
IIa
TFPI
Cross-over reaction
ExtrinsicCascade
IntrinsicCascadeCommonCascade
Must know

6. Secondary Hemostasis
• Prothrombin time (PT/INR):
– Citrated plasma + Ca2+ + phospholipid + tissue factor → √ the time to clot
– Sensitive to factors I, II, V, VII, X (extrinsic & common pathways).
– International normalized ratio (INR) =
– ISI (International Sensitivity Index) = 1.0 to 2.0 (reflects tissue factor activity)
• Activated Partial thromboplastin time (aPTT):
– Citrated plasma + Ca2+ + phospholipid + silica → √ the time to clot
– Sensitive to factors I, II, V, VIII, IX, X, XI, XII (intrinsic & common pathways).
• Thrombin time (TT):
– Citrated plasma + Ca2+ + phospholipid + thrombin → √ the time to clot
– Sensitive to factor I (fibrinogen) and heparin (anti-thrombin).
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Must know

7. ↑Thrombin Time (↑TT)
aPTT 55.6 sec (normal, 35.2 - 40.4), PT 23.2 sec (normal,
12.2 - 14.6), TT 21.4 sec (normal, 9.2 - 12.3)
PTPTT
TTprothrombin thrombin
(IIa)
fibrinogen
fibrin
prothrombinase complex
(X, V, PL, Ca2+
)
tissue factorVII
IX
XI
VIII
XII
7
↑Thrombin time (TT) = ↓Fibrinogen (hypofibrinogenemia) or
presence of heparin
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Must know

8. ↑Prothrombin Time (↑PT)
aPTT 35.6 sec (normal, 35.2 - 40.4), PT 23.2 sec (normal,
12.2 - 14.6), TT 11.4 sec (normal, 9.2 - 12.3).
PTPTT
TTprothrombin thrombin
(IIa)
fibrinogen
fibrin
prothrombinase complex
(X, V, PL, Ca2+
)
tissue factorVII
IX
XI
VIII
XII
8
↑PT with normal aPTT and TT = factor VII deficiency
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Must know

9. ↑aPTT
aPTT 75.6 sec (normal, 35.2 - 40.4), PT 13.2 sec (normal,
12.2 - 14.6), TT 11.4 sec (normal, 9.2 - 12.3).
PTPTT
TTprothrombin thrombin
(IIa)
fibrinogen
fibrin
prothrombinase complex
(X, V, PL, Ca2+
)
tissue factorVII
IX
XI
VIII
XII
9
↑aPTT with normal PT and TT = factor XII, XI, IX, or VIII
deficiency
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Must know

10. A 10-year-old healthy boy with ↑aPTT on a pre-op testing
↑aPTT, corrected with 1:1 mixing of patient plasma with normal plasma
+ ↓factor XII → Factor XII deficiency (clinically insignificant).
Must know
Note: ↑aPTT due to anti-phospholipid antibodies do not correct with the mixing
study. These antibodies do not cause bleeding and the prolonged aPTT would be
clinically insignificant.
Two Limitations of the aPTT Test

11. aPTT 75.6 sec (normal, 35.2 - 40.4), PT 32.2 sec (normal,
12.2 - 14.6), TT 11.4 sec (normal, 9.2 - 12.3).
PTPTT
TTprothrombin thrombin
(IIa)
fibrinogen
fibrin
prothrombinase complex
(X, V, PL, Ca2+
)
tissue factorVII
IX
XI
VIII
XII
11
↑PTT and ↑PT with normal TT = factor II, V, or X deficiency (e.g.,
vitamin K deficiency which ↓factors II, VII, IX, & X)
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Must know ↑aPTT & ↑PT

12. Hemostatic Evaluation
• Detailed bleeding history
• Platelet count
• Platelet function screen
• vWF antigen (vWf:Ag) and activity (vWf R:Co)
• Blood group
• aPTT, PT/INR, TT
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13. a) Factor VIII deficiency
b) NSAID
c) Vitamin K deficiency
d) von Willebrand disease
e) Hypofibrinogenemia
f) Factor VII deficiency
1. ↑Collagen-epinephrine + ↑Collagen-ADP
2. ↑Collagen-epinephrine + nl Collagen-ADP
3. ↑aPTT, nl PT, nl TT
4. aPTT, ↑PT, nl TT
5. ↑aPTT, ↑ PT, ↑TT
6. ↑aPTT, ↑ PT, nl TT
“Must Know Pearls”
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14. Q. A 22-year-old female patient is diagnosed with vitamin K
deficiency.
Which of the following is the most likely finding on her hemostatic
evaluation?
A. ↑PT, ↑aPTT, nl TT
B. nl PT, ↑aPTT, nl TT
C. ↑PT, nl aPTT, nl TT
D. ↑PT, ↑aPTT, ↑TT
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A 23-year-old patient presents to the clinic for menorrhagia. Her
evaluation reveals a normal platelet count, thrombin time (TT),
prothrombin time (PT), activated partial thromboplastin time
(aPTT), von Willebrand factor antigen and activity, and platelet
function screen. Her older sister has a history of heavy menstrual
bleeding and delayed postpartum bleeding. Further testing shows
increased fibrinolysis.
Which one of the following laboratory findings is most likely to be
found in this patient?
A. Decreased plasminogen
B. Decreased plasminogen activator inhibitor-1 (PAI-1)
C. Increased α2-antiplasmin
D. Increased thrombin-activatable fibrinolysis inhibitor (TAFI)
E. Decreased tissue factor pathway inhibitor (TFPI)

16. Comments
This patient has menorrhagia and ↑ fibrinolysis due to ↓ “plasminogen activator
inhibitor-1” (PAI-1). ↓Plasminogen, ↑α2-antiplasmin, ↑thrombin-activatable fibrinolysis
inhibitor (TAFI), and ↓TFPI are not associated with bleeding. Plasminogen plays an
important role in fibrinolysis; it is converted to plasmin, which converts fibrin into fibrin
degradation products (FDPs). Activators of plasminogen are tissue plasminogen
activator (tPA) and urokinase plasminogen activator. Inhibitors of plasminogen are PAI-
1, which regulates tPA and urokinase plasminogen activator, and α2-antiplasmin.
Thrombin-activatable fibrinolysis inhibitor (TAFI) inhibits the conversion of fibrin to
FDPs. PAI-1 deficiency is autosomal recessive (OMIM#173360; serpine1, serpin
peptidase inhibitor, clade e (nexin, plasminogen activator inhibitor type 1), member 1).
A complete deficiency of PAI-1 is associated with mild-to-moderate mucocutaneous
bleeding. The diagnosis is made by measuring PAI-1 activity and antigen and detecting
mutations in SERPINE1. Treatment is plasma + antifibrinolytics (aminocaproic acid,
tranexamic acid).
Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med. 2008; 359(9):938-949.
Heiman M, Gupta S, Khan SS, Vaughan DE, Shapiro AD. Complete plasminogen activator inhibitor 1
deficiency. GeneReviews. PMID: 28771291
Rijken DC, Lijnen HR. New insights into the molecular mechanisms of the fibrinolytic system. J Thromb
Haemost. 2009;7:4-13.

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