Module 4: Disorders of Hemostasis (from module) Flashcards Preview

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Flashcards in Module 4: Disorders of Hemostasis (from module) Deck (40):
1

Summary: Vascular and extravascular disorders

Acquired:
senile purpura
simple easy bruising
secondary vascular purpuras

Inherited:
hereditary hemorrhagic telangiectasia
Ehlers-Danlos syndrome

2

Summary: Platelet disorders - Quantitative (affects # of platelets)

Thrombocytopenia (due to decreased production or increased destruction/utilization)
Thrombocytosis (primary and secondary)

3

Summary: Platelet disorders - Qualitative (affects function of platelets)

Primary (thrombopathies, thrombasthenia, Bernard-Soulier syndrome)
Secondary (drugs, uraemia, abnormal proteins, myeloproliferative disorders, von willebrand disease)

4

Summary: Coagulation disorders

Inherited: Hemophilia A, von Willebrand Disease, christmas disease, liver disease

Acquired: massive transfusion syndrome, abnormal circulating anticoagulants, it K deficiency, DIC

5

Summary: Disordered Fibrinolysis

Primary
Iatrogenic
Secondary Fibrinolysis
Impaired

6

Summary: Thrombosis and Thromboembolism

Inherited: protein C or protein S deficiency, homocysteinuria, dysfibrinogenemia, protein C resistance

Acquired: Lupus anticoagulant, kidney nephrosis, some leukemias, surgery, trauma

7

Vascular and extravascular disorders due to defect

in structure or function of vascular endothelium or sub endothelium

8

Symptoms of vascular and extravascular disorders

petechiae, mucosal bleeding and easy bruising

9

Lab finding of vascular and extravascular disorders

Bleeding time - prolonged
Closure time - prolonged
Capillary fragility tests - positive
Platelet count - normal
PT - normal
APTT - normal

10

Senile purpura (acquired vascular disorder)

bruising in the aged due to atrophy and degeneration of sub endothelium connective tissue

11

Causes of secondary vascular purpuras (acquired vascular disorder)

Endothelial damage due to:
Immune damage
Uremia
Hypertension
Vit C deficiency
Infective organisms, endotoxins
Mechanically induced hypoxia
Increased pressure
Steroid drug administration
Cushing disease
Chronic liver infection/disease
Henoch-Schoenlein Syndrome

12

Hereditary Hemorrhagic Telangiectasia (inherited vascular/extravascular disorder)

AKA HHT or Osler-Weber-Rendu Disease
Autosomal dominant defect in collagen:
dilations of capillaries
Petechiae
Spontaneous bleeds from mucous membrane

Most common inherited vascular disorder but still very rare
15% of HHT victims have AV fistulas
60% of people with AV Fistulas have HHT

13

Ehlers-Danlos Syndromes (inherited vascular/extravascular disorder)

loss of elasticity in epidermis and sub-epidermal tissues

14

Marfan Syndrome (inherited vascular/extravascular disorder)

defect in chromosome 15
abnormal fibrillan in connective tissue and weakness
Aortic prolapse

15

Osteogenesis Imperfecta (inherited vascular/extravascular disorder)

defective collagen formation characterized by bones that break easily

16

Homocystinuria (inherited vascular/extravascular disorder)

disorder of the metabolism of the amino avid methionine

17

Pseudo Xanthoma Elasticum (inherited vascular/extravascular disorder)

disorder of elastin in which elastic tissues in body become mineralized (esp with calcium)

18

Quantitative disorders of platelets - Thrombocytopenia

most common single cause of abnormal bleeding
decrease in PLT

19

Clinical findings in thrombocytopenia

skin purpura (bruising and petechiae)
Mucosal hemorrhages
Increased bleeding after trauma; nose bleeds

20

Lab findings for ALL types of thrombocytopenia

Platelet count - decreased below 150 x 10^9/L
Bleeding time - prolonged
Closure time - prolonged
Clot retraction - poor (less than 50%)

21

Etiologic classification of thrombocytopenia

decreased or ineffective production of platelets
increased destruction or utilization of platelets
Abnormal distribution of platelets

22

Decreased or ineffective production of platelets (2 causes)

Marrow hypoplasia
Ineffective megakaryopoiesis

23

About Marrow hypoplasia

causes pancytopenia (all cells are decreased)
Inherited or acquired
Overcrowding or replacement of normal cells in the marrow (acute leukaemia, myelofibrosis)

Lab findings: low PLT counts
decreased megakaryocytic in bone marrow
Few (if any) megathrombocytes in PBS

24

About Ineffective megakaryopoiesis

megakaryocytes fail to survive or to normally release platelets

Lab findings: low PLT counts
normal looking marrow

25

Increased destruction or utilization of platelets (3 causes)

Excessive consumption of platelets (TTP, DIC, HUS)
Platelet antibodies
Transfusions

26

About excessive consumption of platelets

condition where there is excessive PLT adhesion, aggregation and coagulation
-Thrombotic Thrombocytopenic Purpura (TTP)
-Disseminated Intravascular Coagulation (DIC)
-Hemolytic Uremic Syndrome (HUS)

27

About Thrombotic Thrombocytopenic Purpura (TTP)

rare, fatal
Caused by deficiency of ADAMTS-13 (enzyme required to break up ultra large von willebrands factors (ULVWF) multimers into smaller, less adhesive multimers)
Congenital or due to ADAMTS-13 autoantibodies
Results in presence of ULVWF in plasma and widespread PLT aggregation

Specific Lab findings: Increased megakaryocytic in bone marrow
Increased megathrombocytes in PBS
Increased PLT aggregation in PBS
Decreased PLT survival

28

About platelet antibodies

Patient produced platelet autoantibodies
Immune THrombocytopenic Purpura (ITP)
-PLT antibody (usually GPIIb/IIIa or GPIB) sensitizes the PLT and causes premature removal by macrophages in spleen

Development usually occurs after viral infection or drugs (or for no apparent reason)
- may be acute (children) or chronic (esp. women 15-50yo)
**Chronic ITP is second most common cause of thrombocytopenia

Specific Lab findings: Increased megakaryocytic in bone marrow
PLT antibody in serum
Decreased PLT survival
PLT count 10-50 x10^9/L

29

About Transfusions

Dilution with PLT poor donor blood (very rare)
donor PLT may be sensitized by PLT antibody formed in the patient after a prior transfusion
PLT may also be lost in extravascular circulation (e.g. heart pump, renal dialyser)

30

About abnormal distribution of platelets

increased Splenic pooling of PLT will reduce the count in the blood
Occurs in conditions that cause splenomegaly

31

Thrombocytosis (quantitative)

Increased PLT count (less common than thrombocytopenia)
>400 x10^9/L
-can happen spontaneously
-Often secondary to order disorder or condition
Give patient aspirin

Lab findings: increased PLT counts with abnormal morphology
Increased Megakaryocytic
Increased red cell fallout in the clot retraction test
Normal or prolonged bleeding time

Thrombocythemia = >1000 x10^9/L

32

Qualitative (functional) defects of platelets

Indicated by skin/mucosal hemorrhage with prolonged bleeding time and normal PLT count

33

Inherited (primary) defects (Qualitative/functional defects of platelets)

Disorders of platelet secretion/release reaction
Thrombasthenia (Glanzmann disease)
Bernard-Soulier Syndrome (BSS)

34

About Disorders of PLT secretion/release reaction

1) Storage Pool diseases (granule defects)
Secondary aggregation disorder
a)Dense granules (storage for ADP, ATP, Ca, serotonin)
b)Alpha granules (storage for proteins)
- deficiency leads to agranular appearance of PLT (termed Gray PLT Syndrome)
-PF3 activity reduced leading to defects in PLT aggregation

2)Primary secretion defect (enzymatic pathway defect)
No quantity or content abnormalities of PLT granules
Defect due to deficiencies of enzymes and messengers that transmit signals from surface receptors to cause the release of granule contents.

LAB FINDINGS: bleeding time prolonged
Normal PLT count

35

About Thrombasthenia (Glanzmann disease)

failure of primary aggregation caused by reduced amounts of the membrane glycoprotein GPIIb/IIIa
Aggregation fails because fibrinogen cannot be bound to PLT membrane

Lab findings: bleeding time greatly prolonged
Clot retraction is defective
PLT adhesion to collegen is normal
PLT aggregation ABNORMAL with ADP, epinephrine, thrombin and serotonin
PLT aggregation NORMAL with ristocetin

36

About Bernard-Soulier Syndrome (BSS)

AKA giant platelet syndrome
Failure of PLT adhesion caused by reduced amounts of GPIb/IX
Adhesion fails because vWF cannot be bound to the PLT membrane
Disorder shows severe subcutaneous, mucosal and visceral bleeding (often fatal)

37

Ristocetin

reagent that forces vwf and GPIb to aggregate platelets

38

2 bleeding disorders in which platelets fail to aggregate with ristocetin

bernard-soulier syndrome
von willebrand disease

39

acquired (secondary) defects

more common than inherited defects
Drugs can cause transient defects in adhesion/aggregation
ASA (acetylsalicylic acid/aspirin); can last 4-7 days
Caffeine, carbenicillin, anti-inflammatory drugs, vasodilators, antihistamines, dextran, alcohol, ampicillin, epinephrine, sulfinpyrazone, heparin

40

How aspirin blocks cyclooxyrgenase (required for plt aggregation)

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