BLEEDING DISORDERS

Question 1

When may normal hemostatic system go wrong?

Answer 1

• failed to form platelet plug

- failed to form fibrin form

Question 2

Why may the platelet plug fail to form?

Answer 2

• vessel wall (missing components)
• platelets (Reduced # or fxn)
• VWF (hereditary d.o-AD)

Question 3

What are some vascular abnormalities?

Answer 3

• MARFAN’S syndrome (valves affected/ lack of collagen in vessels/ hyperflexibility)
• ac

Question 4

Name an acquired cause of vasculitis.

Answer 4

• –Henoch-schonien purpura (in kids)
• —-viral
• —-could be ITP too
• —presents as PR bleeding AND mucosal bleeding

Question 5

Which vitamin deficiency results in vasculitis?

Answer 5

• Vitamin C deficiency
• – Scurvy
• –particularly seen in lower limbs, fundi, chest if coughing

Question 6

Senile purpura

Answer 6

Iary hemostasis

Question 7

Commonest cause of acquired thrombocytopenia.

Answer 7

• incr. DESTRUCTION of platelets

- more common in YOUNGER kids

Question 8

WHcih 2 conditions use up platelets?

Answer 8

DIC

ITP

Question 9

When is DIC seen

Answer 9

• d.t MASSIVE TISSUE damage

- —-RTA/ Wrong blood transfusion/ malignancy/ OBSTETRIC complication

Question 10

What is an automimmune cause of peripheral platelet destruction?

Answer 10

ITP: Immune thrombocytopenic Purpura
SLE

—-isoimmune (post-transfusion and neonatal)

Question 11

Causes of platelet fxn defects.

Answer 11

• Hereditary: surface lipoproteins missing

- Acquired (drugs - NSAIDs/ ASPIRIN/// Renal failure)

Question 12

How does vWF def. present as?

Answer 12

Herditary or ACQUIRED

Hereditary:

• —AUTOSOMAL dominant
• common
• generally mild

Question 13

Acquired causes of thrombocytopenia?

Answer 13

• Reduced prodn (marrow failure)

- incr. destruction

Question 14

What could go wrong in IIary hemostasis?

Answer 14

1. Multiple clotting factor defi. : could be used (DIC in sepsis
2. single clottign factor deficiency (failure of prodn—hereditary= Hemophilia A (VIII)

Question 15

WHat conditions result inmultiple clotting factors def.?

Answer 15

• LIVER FAILURE (fatty liver disease/Iary biliary cirrhosis)
• Vitamin K def. ( warfarin therapy) —–2, 7,9,10
• complex coagulopathy (DIC)

Question 16

Which clotting factors REQUIRE vitamin K for prodn?

Answer 16

FACTORS 2, 7, 9, 10

they are carboxylated by Vit K; ESSENTIAL FOR FUNCTION

Question 17

WHere is vitk sourced from?

Answer 17

• diet

- intestinal synthesis

Question 18

Why are vit. K shots given to bbies?

Answer 18

—risk of hemorrhagic disease of the newborn

Question 19

What is REQUIRED for Vit. K absorprtion?

Answer 19

• requires bile SALTS for absorption in the UPPER intestine

Question 20

Causes of Vit. K deficiency.

Answer 20

• warfarin
• obstructive jaundice
• malabsorption
• poor dietary intake
• hemorrhagic disease of newborn

Question 21

How does DIC occur?

Answer 21

1. DUE TO MASSIVE tissue damage> Excessive and inappropriate activation of haemostatis system - exposure of TF to vascular components
2. TO COUNTERACT 1., MICROVASCULAR thrombus formation occurs. (> tissue infarction> END organ failure)
3. With continuous 1, and 2 > clotting factor consumption —> BRUISING, PURPURA and generalized bleeding

Question 22

LIVER DISEASE and warfarin disease appears how so in bleeding screening test?

Answer 22

-PT and APTT both LOWERS
—PT is first to lower ——V. GOOD to monitor liver disease
(VII is first to go)

Question 23

How may SEPSIS cause DIC?

Answer 23

• DIRECT bacterial damage and hypoxia (ENDOTOXEMIA- endotoxins trigger the RELEASE of tissue factor from the monocytes)

Question 24

How may DIC be triggered in obstetric emergencies?

Answer 24

====placenta contains a HIGH amount of tissue factor or thromboplastic factors; so in placental abruption, DIC is greatly triggered

Question 25

What malignancies cause DIC? How?

Answer 25

- ---slowly, progressive develop. of DIC# - ---ADENOCa (Bowel and prostate cancer) - --by release of proteolytic enzymes and expression of tissue factor - ---more thrombotic fts

Question 26

How to treat DIC?

Answer 26

1. treat underlying cause 2. replacement therapy - platelet/ plasma/ fibrinogen (cryprecipitate) replacement

Question 27

How may bleeding in to the joints in hemophilia occur?

Answer 27

Spontaneous haemorrhages occur in tissues that are subject to MECHANICAL stress > bleeding into joints> IRON in blood irritate the synovium > triggers the neovascuralisation in the synovium >easily broken vessels

Question 28

Hemophilia is associated with

Answer 28

- LARGE and medium blood vessels

Question 29

What are the 3 types of haemophilia? And how does it indicate VIII/IX levels?

Answer 29

- mild (<2%) - moderate (2-5%) - severe (>5%)--

Question 30

What is prolonged in haemophilia?

Answer 30

- APTT

Question 31

What are the clinical fts of severe haemophilia?

Answer 31

- recurrent haemarthroses (start at 2/3 years) - recurrent soft tissue bleeds (bruising in toddlers) - --- prolonged bleeding after dental extraction/ surgery

Question 32

How to manage Haemophilia A?

Answer 32

- IV Factor VIII every second day - self administered - ---prevent massive bleeds

Question 33

What occurs with reccurent joint bleeds!

Answer 33

- reccurent bleeding results in HAEMARTHROSES | - ----affects MOTIBILITY of joint!

Question 34

What is the commonest cause of PRIMARY haemostatic failure?

Answer 34

thrombocytopenia!

Question 35

How does vWF def. present as?

Answer 35

----menorrhagia/ bleeding gums/ nose bleeds

Question 36

What is the MOST COMMON hematological manifestation of AIDS?

Answer 36

thrombocytopenia!

Question 37

Which infections causes thrombocytopenia?

Answer 37

MEASELS AIDS -----BOTH said to IMPAIR prodn of platelets!

Question 38

What drugs cause thrombocytopenia?

Answer 38

IMPAIRS prodn: cytotoxic drugs/ thiazides/ alcohol Immune destruct.: Quinidine/ Heparin/ Sulfa compounds

Question 39

When may ineffective megakaryopoiesis occur? What does this result in?

Answer 39

with MEGALOBLASTIC anaemia and paroxysmal nocturnal hemoglobinuria ----thrombocytopenia.

Question 40

In whom is haemophilia seen in?

Answer 40

MEN | - X-linked, hereditary d.o

Question 41

Which haemophilia type is MORE common?

Answer 41

``` Haemophilia A (5x more common) -----VIII deficiency ```

Question 42

What causes non-immunological destruction of platelets?

Answer 42

1. thrombotic thrombocytopenic purpura 2. DIC 3. Giant hemangiomas 4. Microangiopathic hemolytic anaemia

Question 43

What is ITP? Best rx?

Answer 43

- Spleen - the MAIN culprit for pathogenesis - ----site of anti-platelet Abs and site of DESTRUCTION of IgG coated platelets RX: if chronic ITP= Splenectomy

Question 44

What does a bone marrow with incr. megakaryocyte, suggest ?

Answer 44

- accelerated platelet destruction | - common to all forms of thrombocytopenia

Question 45

What is the risk of heparin? | WHy does it occur?

Answer 45

- drug- induced thrombocytopenia (sets in 1/2 weeks after administration) - ---seen more with UNfractionated heparin. ---d.t formation of IgG abs activating platelets !

Question 46

How is the dx of hemophilia made? How is it treated?

Answer 46

- using specific assays of Factor VIII and IX | - infusion of recombinant factor VIII and IX

Question 47

Why is splenomegaly a problem?

Answer 47

- chronically enlarged spleen often removes single/ multiple elements of the blood > thrombocytopenia (common), anaemia, leukocytopenia

Question 48

What are the key roles of vWF?

Answer 48

1. carrier of Factor VIII | 2. binds platelets to endothelium and other platelets; def. ==> poor aggregation of platelets

Question 49

WHat is seen with the lab results of vWF disease?

Answer 49

- raised Bleeding time | - may have slight rise in PTT (if SEVERE; factor VIII is a.w vWF)

Question 50

What occurs in Heyde's Disease?

Answer 50

- GI bleeding in the setting of Aortic stenosis. d.t 2 reasons: 1. Incr. in vascular malformations in the GI tract (PRONE to bleeding) 2. def. of vWF (HIGH sheering force through aortic stenosis UNCOILD vWF multimers; exposing it to ADAMTS13 enzyme) ---basically an OVERACTIVITY of ADAMTS 13