1
Q
What is placed in samples of blood and why?
A
- blood sample in sky blue cap
- SODIUM CITRATE –> halts coagulation process and preserves coagulation factors (by blocking calcium)
2
Q
What is normal bleeding time?
A
<10 mins
3
Q
What does prothrombin time (PT) measure and when is it prolonged?
A
- tests extrinsic and common pathway
- prolonged in acquired disorders:
- vit. K deficiency
- liver disorders
- warfarin Tx.
4
Q
What is INR?
A
International Normalised Ratio
- standardised PT value
- correction for different thromboplastin reagents used (animal product)
5
Q
What does an INR of 1 mean?
A
-pts. plasma has the same extrinsic pathway as that of a normal plasma corrected for various commercial reagents
** high INR = longer it takes for blood to clot
6
Q
What is suspected if both PT + PTT are increased?
A
pathology is in the COMMON pathway
7
Q
What does partial thromboplastin time (PTT) measure and when is it prolonged?
A
- intrinsic + common pathways
- prolonged in congenital bleeding disorders
- hemophilias (A + B)
- von Willebrand disease
8
Q
When is thrombin time performed and what does it test?
A
- when both PT + PTT are abnormal
- tests fibrinogen levels (COMMON pathway)
- *useful in DIC
9
Q
When is FDP/D-Dimer increased?
A
DIC (clot breakdown occurring)
10
Q
What are the test priniples for PT + PTT?
A
PT:
-animal tissue thromboplastin (with sodium citrate) –> FVIIa –> CLOT
PTT:
-kaolin + cephalin –> FXIIa –> FVIIIa/FIXa –> CLOT
11
Q
What is suspected if a pts. plasma with increased PT/PTT is mixed with normal plasma and the PT/PTT corrects?
A
clotting factor deficiency
12
Q
What is suspected if pts. plasma with increased mixed with normal plasma and the PT/PTT does not correct?
A
- PT/PTT inhibited
- therefore –> coagulation inhibitors
i.e. heparin; specific factor inhibitor (FVIII or FV); non-specific inhibitor (lupus anticoagulants)
13
Q
What is a thromboelastogram (TEG)?
A
- quick test before and during major surgery
- measures clot formation, strength + lysis
- global assessment of hemostatic function
14
Q
What are the lab. findings (Plt count, BT, PT, PTT) for common hemostatic disorders:
- ITP?
- vWD?
- Hemophilia?
- DIC?
- Aspirin?
- Warfarin/Heparin?
A
ITP:
- plt count –> low
- BT –> high
- PT –> normal
- PTT –> normal
vWD:
- plt count –> normal
- BT –> high
- PT –> normal
- PTT –> high
Hemophilia:
- plt count –> normal
- BT –> normal
- PT –> normal
- PTT –> high
DIC:
- plt count –> low
- BT –> high
- PT –> high
- PTT –> high
Aspirin:
- plt count –> normal
- BT –> high
- PT –> normal
- PTT –> normal
Warfarin/Heparin:
- plt count –> normal
- BT –> normal
- PT –> high
- PTT –> high
15
Q
Where is vWF located and what does this mean for its function?
A
Subendothelial region
-aidss plt. adhesion to endothelial defects
Plasma
-carries FVIII and prevents early degeneration
16
Q
Clinically, what is the commonest bleeding disorder?
A
Thrombocytopenia
-commonest cause of bleeding
17
Q
Outline plt production
A
thrombopoietin stimulates endomitotic synchronous nuclear replication of megakaryocytes –> cytoplasmic granulation –> cytoplasmic fragments separate out as platelets (loaded w coag. factors)
18
Q
What is the lifespan of plts and what results afterwards?
A
8 - 9 days
-either involved in hemostasis
OR
-destroyed in spleen
19
Q
Describe typical bleeding characteristics in thrombocytopenia
A
-superficial bleeding (capillary damage)
Clinically:
- petechiae
- purpura
- ecchymosis
20
Q
What hemostatic factors are contained in platelets?
A
- ADP
- calcium
- vWF
- PF4
- fibrinogen
21
Q
What are the causes of thrombocytopenia?
A
- autoimmune, drugs, infections - viral
- BM suppression
- megaloblastic anemia
- aplastic anemia
- increased consumption (DIC, TTP + HUS)
- Plt function disorders: - less common
- vWD, Bernard Soulier syndrome, Glauzman thrombasthenia
- plts are present but NOT functional
22
Q
What is normal plt. count and what counts result in excess + spontaneous bleeding?
A
normal: 150 - 250 x 10^9/L
excess bleeding: <50 x 10^9/L (i.e. after trauma/surgery)
spontaneous bleeding: <20 x 10^9/L (severe and life-threatening)
23
Q
What is ITP and what are the clinical features?
A
- immune thrombocytopenic purpura
- autoimmune disorder –> IgG Ab against plts –> plts destroyed in spleen –> thrombocytopenia
CF’s:
- petichiae
- purpura
- ecchymosis
- easy bruising
24
Q
What are the 2 types of ITP?
A
- acute
- children, post-infection, self-limited - chronic
- F (20-40yrs)
- chronic + severe
25
What are the lab. findings in ITP?
CBC:
- thrombocytopenia
- giant immature plts
PT/PTT:
-normal (coagulation is normal)
BM:
-immature megakaryocytes increased --> compensatory in response to loss of plts.
26
What are the common causes of viral haemorrhagic fevers and what is the pathogenesis?
Causes:
-dengue, chikungunya, measles, malaria, yellow fever, Ebola, etc
Patho:
-endothelial damage by virus +/or anti-viral Abs --> vasculitis --> plt. activation --> thrombocytopenia --> bleeding
*PT/PTT usually normal
27
What coag. factor deficiency is present in hemophilia A + B?
A --> FVIII
| B --> FIX
28
What type of genetic abnormality is hemophilia + what does this mean?
x-linked recessive
- increased in females (carriers)
- increased in males (affected)
29
True or False?
| -hemophilia A/B results in petichiae/purpura/ecchymosis
False
- as coag. factors (NOT plts) are affected, bleeding is deep NOT superficial
- increased wound bleeding and deep hematoma
- joint bleeds (skin/mucosal bleeding in severe)
30
What is the therapy for hemophilia?
DDAVP
-releases factors from endothelium
FVIII/FIX concentrate
31
Where is vit. K found and what is it necessary for?
- green leafy veggies + intestinal bacteria
| - necessary for carboxylation of factors 2, 7, 9, 10 in the liver
32
What are the causes of vit. K deficiency?
- diet
- drugs
- liver disease
- warfarin inhibits vit. K action (to prevent thrombophilia)
33
Why is PT increased and PTT normal until late in vit. K deficiency/warfarin Tx.?
-factor VII (extrinsic pathway - PT) has the shortest half-life --> warfarin affects this factor first
34
What is vWD?
- von willebrand disease
- low vWF --> deficiency of both platelet adhesion to damaged endothelium AND deficiency in FVIII
- both plt. and coag. = abnormal --> superficial and deep bleeds
35
What is vWF produced by?
both plts. and endothelial cells
36
True or False?
| -vWD is an x-linked recessive disorder
False
- autosomal dominant
- both males + females affected
37
Why is there increased BT despite normal plt. count in vWD?
- low vWF in vWD
| - plts cannot function without vWF (cannot bind to collagen in endothelial defects) --> increased BT
38
Why is normal PT but PTT increased in vWD?
- vWF carries + protects FVIII
| - no vWF in vWD = FVIII deficiency --> increased PTT
39
What is therapy for vWD?
fresh frozen plasma (FFP)/cryoprecipitate which contain vWF
40
What is DIC?
Disseminated Intravascular Coagulation
| -systemic activation of coagulation --> consumption of coag. factors + plts --> severe bleeding
41
What is the cause/etiology of DIC?
-infection/trauma/cancer
-release of tissue factor into circulation --> trauma
OR
-widespread endothelial damage --> infection
42
What is the pathogenesis of DIC?
activation of coagulation --> microthrombi --> infarction --> consumption of hemostatic factors --> bleeding --> activation of fibrinolysis --> excess fibrin breakdown
43
What are the clinical features of DIC?
- thrombosis
- severe bleeding
- shock
- renal failure
44
What are lab Dx. for DIC?
- decreased coag. factors (deep) + plts (superficial) --> ALL tests abnormal
- FDP + D-Dimer increased
* life-threatening
45
What are the 2 clinical syndromes of thrombotic microangiopathy? and how do they differ to DIC?
1. thrombotic thrombocytopenic purpura (TTP) - adults
2. hemolytic uremic syndrome (HUS) - children
- unlike DIC, coagulation factors remain normal or mild decrease
- ONLY activation of plts.
46
What is thrombotic microangipathy?
- widespread thrombosis in microcirculation leading to organ infarctions + microangipathic hemolytic anemia (fragmented RBCs)
* TTP + HUS
47
What are the predominant consequences of TTP + HUS?
TTP --> neurologic defects/strokes
| HUS --> kidney failure
48
What enzyme is deficient in TTP? What is its normal function and how can one be deficient in it?
ADAMTS13
- protease which normally breaks down vWF multimers to stop plt activation
- essentially, TTP is opposite to vWD as there is increased vWF --> increased plt. activation + loss --> extensive systemic thrombosis
Acquired:
-Ab to ADAMTS13 --> deficiency
Congenital:
-mutation --> ADAMTS13 deficiency
49
How is TTP treated?
-plasma exchange with fresh frozen plasma or cryoprecipitate to remove Ab or replace ADAMTS13 (previously 90% fatal)
50
True or False?
| ADAMTS13 levels are decreased in childhood HUS
False
- normal levels
- E. coli/shigella infection + shiga toxin causing extensive endothelial damage --> plt activation
51
What is adult HUS?
TTP with predominant renal failure
52
What are the natural anticoagulants?
Protein C + S --> inhibit FVIIIa + FVa
| Heparin --> inhibits thrombin (FIIa)
53
What is the most common anticoagulant drug + what does it inhibit?
warfarin
- inhibits vit. K reductase
- decreased vit. K dependent coag factors (2, 7, 9, 10)
54
What are the hereditary causes of hypercoagulability?
Factor V Leiden mutation
- Factor V is resistant to protein C inhibition
- uncontrolled factor V activation
Protein C/S deficiency
-decreased inhibition of FVa + FVIIIa
55
What are acquired causes of hypercoagulability?
- trauma, inflamm., cancer
- heart disease, atherosclerosis, HTN, DM, etc
- stasis of blood
- drugs, Abs --> antiphospholipid antibody syndrome (AAS)
* *Virchow's Triad (Blood - BV - Blood Flow)
56
What are clinical features of hypercoagulability?
THROMBOSIS
- vein --> DVT (potential PE)
- artery --> thrombosis; stroke
- placenta (pregnancy) --> abortion
57
What is AAS + what Abs are involved?
antiphospholipid antibody syndrome
- Abs to plt. phospholipids:
1. anticardiolipin
2. lupus anticoagulant
N.B. following infection in children/pts with autoimmune dis./drugs
58
What % of SLE pts develop AAS?
30%
59
How does AAS differ clinically from in the laboratory?
- clinically, autoantibodies activate coagulation in body
| - in lab. autoantibodies bind to phospholipid part of reagent --> prolong PTT
60
What is the lab Dx. of AAS?
- normal PT but prolonged PTT --> looks like deficiency but is hypercoagulability
- PTT remains prolonged even after adding 50% normal plasma --> unlike factor deficiency
61
What is contained in fresh frozen plasma + cryoprecipitate and what are the indications for transfusion?
FFP --> all coag. facotrs --> bleeding
cryoprecipitate --> factor 1, 8, 9, vWF --> specific deficiency
*factor 1 = fibrinogen
62
What is the shelf-life of platelet concentrate?
5 days
63
Why are RBCs easier to match in transfusions compared to WBCs/plts?
WBCs/plts
- have HLA Ag
- difficult to match
- more reactions/rejections
RBCs
- no HLA Ag
- only major blood groups
64
What are the clinically significant blood group systems + why?
ABO + Rh
| -naturally occurring strong IgM antibodies
65
What is the commonest + rarest blood group?
```
commonest = O+
rarest = AB-
```
66
What is Landsteiner Law?
when a person has a blood group Ag, corresponding Ab is ABSENT from plasma
67
What is the substance known as on red cell membranes that is modified by A, B, O genes?
H substance
| -A, B, O genes control synthesis of enzymes that modify red cell membrane glycolipid (H substance)
68
What are the 3 genes involved in Rh system?
1. C/c
2. D/d
3. E/e
Rh+ = D --> strong/clinically significant
Rh- = d
-little letter denotes negative
69
What is bombay blood group?
- absence of H substance in ABO blood system
- anti-H antibodies present
- clinically seen as O group
70
Compare IgG vs. IgM
IgG:
- small, monomer
- optimum reaction @37degrees
- able to cross placenta
- coat cells --> no agglutination
- main type produced following preg./transfusion (alloantibodies)
IgM:
- large, pentamer
- optimum reaction @-20degrees
- does NOT cross placenta
- agglutinates
- often "naturally occuring" Abs - ABO blood group
71
What is a major + minor cross match?
```
major = donor RBC with pt. plasma
minor = donor plasma with pt. RBC
```
--> to prevent hemolytic transfusion reaction
72
What is the purpose of Ab screening?
- many other Ags on donor RBC
- additional Ab screening done to detect alloantibodies in pt. plasma with known reagent RBC (post transfusion/pregnancy)
73
What are the 3 main transfusion reactions and what are each caused by?
1. allergic --> plasma proteins
2. febrile --> Abs to donor leucocytes
3. hemolytic --> immune/mismatch
74
What are the Sx. of hemolytic transfusion reaction?
- hemoglobinuria
- chest pain
- apprehension
- lower back pain
- fever/chills
- decr. BP/incr. RR
- acute kidney failure*
75
Why is bacterial contamination of blood products more common with plts?
They are kept at increased temp. (22degrees)
76
What is "lookback program"?
-identify + notify recipients of blood products from previously negative/screened donor who is now positive for infectious agent
Pathology Term 3
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