Heme/lymph - Dr. K Khin: Bleeding Disorders

Front 1

Bleeding stoppage requires:

Back 1

1. BV contraction
2. platelet adhesion
3. plug formation
4. plasma

Front 2

Hemorrhaging occurs when:

Back 2

coagulation factors are not functioning properly

Front 3

Where is factor VIII made?

What does it complex w?

Back 3

kidney and liver

complexes w/ vWF (von Wilebrand factor)

Front 4

What attaches to activated vWF?

Where?

Why?

Back 4

platelets

at injury site

to form platelet plug/aggregate w/ fibrin

Front 5

What are hemorrhagic diseases due to increased vascular fragility:

1. congenital
2. acquired?

Back 5

1. a) Osler-Weber-Rendu disease
b) Ehlers-Danhlos disease

2. a) Henoch-Scholein Purpura
b) infxns & drugs
c) misc

Front 6

What are the clinical presentations of bleeding due to vascular disorders?

Back 6

petechial & purpuric hemorrhages in skin and GI/GU tracts

occasional hemorrhages into jts, mm & subQ tissue

Front 7

What is found to be nL in hemorrhages due to inc vasc fragility?

Back 7

1. platelet count
2. coagulation time
3. bleeding time

Front 8

Osler-Weber-Rendu disease:
1. aka
2. describe it
3. where are petechiae often noted?

Back 8

1. Hereditary hemorrhagic telangiectasia
2. microvascular dilatations in skin, mucosa and GIT
3. lips & tongue

Front 9

Define telangiectasia

Back 9

small, dilated BVs

Front 10

Ehlers-Danhlos disease

Back 10

inherited mesenchymal defect

with

impaired formation of collagenous support of BV walls

Front 11

Henoch-Scholein purpura

Back 11

- allergic purpura a/w jt p & GIT symptoms

- generalized vasculitis w/ deposition of immune complexes in BVs & w/in glomerular mesangial regions

Front 12

Tetrad a/w Henoch-Scholein purpura

Back 12

GAAP
glomerular nephritis
abd pain
arthritis
purpura

Front 13

what in Henoch-Scholein purpura can lead to renal failure?

Back 13

deposition of immune complexes

Front 14

Describe how a) infections & b) drugs can lead to hemm ds due to inc vascular fragility?

Back 14

a) capillary damage may follow bacT or viral infxn (meningococcemia, severe measles)

b) drug induced Abs w/ deposition of immune complexes can also produce vasc damage

Front 15

What are the misc causes of hemm ds due to inc vasc fragility?

Back 15

integrity of vessel walls weakened in:

1. cushing's syndrome
2. protein starvation
3. scurvy
4. old age (senile purpura)

Front 16

what are the 2 categories of hemorrhagic diseases due to reduced platelet #?

Back 16

1. dec platelet production
2. dec platelet survival

Front 17

thrombocytopenia

Back 17

reduction of blood platelets to >150,000/cu.mm

- spont bleeding occurs when platelet count falls to 10,000-20,000

- bleeding usually petechial --> seen in skin, MM & saerosal surfaces

- occurs immed after trauma or surg procedure

Front 18

reduction in platelet production can be due to?

Back 18

1. aplastic anemia
2. s/p therapy w/ marrow-depressive drugs
3. massive infiltration of marrow w/ leukemic or other malignant cells
4. drug-induced thrombocytopenia (thiazides, cytotoxic drugs)

Front 19

4 types of dec platelet survival?

Back 19

1. immunogenic rxn to drugs - quinine, quinidine
2. infxns - IM, HIV
3. auto0immune: e.g. ITP, SLE
4. consumption - DIC, TTP, MAHA

Front 20

where does sequesteration of platelets occur?

Back 20

spleen - hyperspleenism

Front 21

dilution

Back 21

massive transfusion of stored blood --> viable platelets depleted in banked blood stored for more than 24 hrs

Front 22

what is the MC hematologic manifestation of AIDS?

Back 22

thrombocytopenia

Front 23

what is thrombocytopenia believed to result in, in AIDS pts?

Back 23

immune-complex mediated injury of platelets and HIV-mediated suppression of megakaryocytes

Front 24

ITP (Idiopathic thrombocytopenic purpura)

Back 24

- presence of platelet IgG Abs on surface of platelets

- platelets reduced, bleeding time (BT) increased

Front 25

ITP:
- what is the spleen a major site of production of?

- what happens in children

- the chronic form usually affects?

- occurs as a 1st manifestation if?

Back 25

- antiplatelet Abs & destruction of IgG-coated platelets

- ds more acute & seen after viral infxn

- young adult women

- SLE

Front 26

ITP:
diagnosis based on:

Back 26

- clinical features
- presence of thrombocytopenia
- inc #s of megakaryocytes in BM

Front 27

what does thrombotic microangiopathies include?

Back 27

1. thromboic thrombocytopenic purpura (TTP)
2. hemolytic uremic syndrome (HUS)

Front 28

thrombotic microangiopathies:
- type of disorder?
- a/w?

Back 28

- rare, acute systemic disorder

- deposition of fibrin-platelet microthrombi in small arterioles & capillaries

Front 29

thrombotic microangiopathies:
- characterized by?
- initiating mechanism?

Back 29

- fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), renal failure, neurologic deficits in TTP
- endothelial injury & activation of intravascular thrombosis

Front 30

HUS?

TTP?

Back 30

- onset in childhood, no neurologic deficits, acute renal failure more predominant feature & usually follow GI infxns

- commonly seen in F, no evidence of previous bacT infxn

Front 31

HUS vs TTP

Back 31

HUS - childhood, no neuro problems, ARF after GI infxn

TTP - in F, no previous bacT infxn

Front 32

hemorrhagic ds due to defective platelets:
-inherited
-acquired

Back 32

inherited:
a) Bernard-Soulier syndrome
b) Glanzman ds

acquired:
drugs - ASA, indomethacin, pheynlbutazone

Front 33

Bernard Soulier syndrome

*board review notes

Back 33

defective platelet adhesion

(defect in platelet plug formation --> decreased Gp1b -> defect in platelet-to-collagen adhesion)

Front 34

Glanzmann's thrombasthenia

*board review notes
*lab findings

Back 34

imapired platelet aggregation

(defect in platelet plug formation --> decreased GpIIb/IIIa -> defect in platelet-to-platelet aggregation)

Labs: blood smear shows no platelet clumping

Front 35

acquired hemorrhagic ds due to defective platelets:

drugs

Back 35

defective release of ADP by platelets

Front 36

Idiopathic thrombocythemia

Back 36

**least common of myeloproliferative disorders

**megakaryotcytic hyperplasia in BM w/ marked platelet production

**inc platelet count w/ GIANT platelets & abnL forms

Front 37

other myeloproliferative disorders

Back 37

CML
polycythemia vera
myelofibrosis

Front 38

hemorrhagic ds due to abnL in clotting factors include:
1. hereditary defects
2. acquired defects of coagulation

Back 38

1.
a) Hemophilia A (factor VIII def; Classical hemophilia)
b) Hemophilia B (factor IX def, Christmas disease)
c) von Willebrand ds

2.
a) vit K deficiency

Front 39

- bleeding due to def in coagulation factors seen as:

Back 39

- large areas of ecchymosis
- hematomas in subQ tissue or mm
- hemorrhage into jts, GI & GU tracts
- prolonged bleeding after sx

Front 40

Hemophilia A
- genetics
- etiology
- mechanism

Back 40

- disorder of M transmitted as X-linked recessive trait

- ~30% of cases due to new mutations and not FH

- **from defective factor VIII (antihemophilic factor)

Front 41

Hemophilia A:
- presentation
- clinical features occur w/

Back 41

- bleed may be spont. (**jts - dec fnxn**) or result from trauma

- severe def: facrot VIII levels <1% of nL

Front 42

Hemophilia A:
- diagnosis
- labs

Back 42

- hx, FH, lab findings

- BT and PT = nL
- platelet count = nL
- PTT = prolonged, corrected by mixing w/ nL plasma
- factor VIII assay required for dx

Front 43

Hemophilia B:
- genetics
- general

Back 43

- X-linked recessive coag disorder

- clinically indistinguisable from hemophilia A but less common; may be asymptomatic or w/ associated hemorrhage

Front 44

Hemophilia B:
- labs
- dx

Back 44

- PTT = prolonged
- BT = nL
- dx possible only by factor IX assay

Front 45

von Willebrand disease
- genetics
- characterized by
- difference w/ hemophilia

Back 45

- autosomal dominant disorder due to qualitative or quantitative defect in vWF

- epistaxis, menorrhagia, rapid onset of abnL bleeding after surgery or trauma

- bleeding into jt space abnL

Front 46

von Willebrand disease
- labs
- clinical

Back 46

- BT = prolonged
- platelet count = nL

- usually mild

Front 47

von Willebrand ds:
Type I

Type II

Back 47

- MC variant, characterized by reduced quantity of circulating vWF

- less common (qualitative defect)

Front 48

what does vWF do?

(relation to von Willebrand Type I)

Back 48

stabilizes factor VIII by binding to it:
dec wWF --> dec factor VIII

Front 49

vit K def

Back 49

- dec factors II, VII, IX, X

- severe liver ds & anticoagulant therapy can cause coagulation defects & severe hemorrhage

Front 50

DIC

Back 50

BT = increased
PT = increased
PTT = increased
platelets = decreased

Front 51

ITP vs TTP

Back 51

ITP = autoimmune; young F/children; IgG abs on platelets

TTP = unknown; only young F; fibrin-platelet microthrombi