L33: Hemostasis Abnormalities Causing Bleeding Flashcards Preview

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Flashcards in L33: Hemostasis Abnormalities Causing Bleeding Deck (33)
1

What are the symptoms of disorders of primary hemostasis?

Bleeding manifests in epithelium (mucocutaneous bleeding)

Skin hemorrhages: petechiae < purpura < ecchymoses

Bleeding after superficial cuts/scratches

Menorrhagia

Gingival bleeding

Epistaxis

GI beeding

2

What are the symptoms of disorders of secondary hemostasis?

Anatomic or soft tissue bleeding

Delayed or recurrent bleeding

Hemoarthrosis

Bleeding into muscle, deep tissues, body cavities

Large ecchymoses or hematomas

3

What laboratory screening tests for hemostasis disorders?

CBC: WBC, HGB, HCT, Retic, PLT, Diff, blood smear

For primary hemostasis: PLT count, bleeding time (increased in VWD, platelet abnormalities and vascular disorders)

For secondary hemostasis: PT (extrinsic and common pathways), APTT (intrinsic and common pathways) and TCT/fibrinogen assay (fibrinogen deficiency)

4

What are the classes of disorders of primary hemostasis?

1. Thrombocytopenia
2. Functional platelet defects
3. Von Willebrand Disease
4. Vascular defects

5

What are the causes of decreased production leading to thrombocytopenia?

Congenital: various inherited diseases; may have physical malformations, anemia, abnormal platelet size or morphology

Acquired:
1) Drugs
2) Viruses: CMV, EBV, varicella-zoster, rubella
3) Myelophthisic: infiltration of bone marrow with abnormal cells
4) Megaloblastic: vitamin B12 or folate deficiency (pancytopenia)

6

Immune thrombocytopenic pupura (ITP)

Causes increased destruction of platelets

Patient forms autoantibody against GP IIb-IIIa

Antibody-sensitized platelets removed by spleen macrophages

Acute form in children post-viral infection and is self-limiting

Chronic form mainly in adults and treated with immunosuppression

Can also treat by splenectomy

7

Drug-induced thrombocytopenia

Causes increased destruction of platelets

Many drugs implicated

Various immune mechanisms

Get autoantibody to plt

8

Nenoatal alloimmune thrombocytopenia (NAIT)

Mother forms IgG allantibody against fetal platelet antigen in early pregnancy

IgG passes plecenta, binds to fetal platelets which are phagocytized by macrophages in the spleen

Similar mechanism to HDFN

9

Posttransfusion purpura

Causes increased destruction of platelets

Pt develops severe decrease in platelets after transfusion due to alloantibody against antigen in transfused platelets

Pts usually have history of exposure to platelet antigens through previous transfusion or multiple pregnancies

Treated w/ immunosuppression or antigen-negative platelets if needed

10

Heparin-induced thrombocytopenia (HIT II)

Causes increased destruction of platelets

Heparin binds to platelet factor IV

Pt develops IgG antibody to heparin-PFIV complex after receiving unfractionated heparin

Immune complex triggers platelet activation and aggregation

Thrombocytopenia occurs 5 - 14 days after starting heparin

Venous thrombosis occurs in 10 - 30% of cases; 20% mortality rate

Tx: discontinue heparin and use a non-heparin anticoagulant

11

HIT I

Non-immune mediated

Mild, rapid, and transient decrease in platelets after heparin administration

Causes some platelet aggregates which are removed from circulation

Is benign

12

What are the non-immune causes of thrombocytopenia? How do they function?

Thrombotic microangiopathies: TTP, HUS, DIC

Thrombi form in blood vessels and rupture RBCs (forming schistocytes) as tehy pass through partially occluded vessels

Thrombocytopenia and anemia

13

Thrombotic thrombocytopenic purpura (TTP)

Acquired TTP involves autoantibody to ADAMTS-13 and inability to cleave ultra ultra-large VWF

ULWF spontaneously bind platelets causing activation and platelet thrombi in microvasculature, obstruction of blood flow to organs, and fragmentation of RBCs (schistocytes)

Triad: thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms (+ fever, renal symptoms)

See decreased HGB, increased retics, increased LD, decreased haptoglobin, hemoglobinuria, and schistocytes in blood smear

Tx: plasma exchange to remove ADAMTS-13 antibody

14

Hemolytic uremic syndrome (HUS)

Acute gastroenteritis (E. coli O157:H7) in young children

Shiga toxin damages endothelial cells causing release of ULVWF and thus platelet thrombi in microvasculature, mainly in the kidney, and RBC fragmentation (schistocytes)

Triad: thrombocytopenia, microangiopathic hemolytic anemia, and renal failure

See decreased hemoglobin, increased retics, increased LD, decreased haptoglobin, hemoglobinuria, schistocytes in smear

Tx: treat renal failure

15

Disseminated intravascular coagulation (DIC)

Systemic activation of coagulation secondary to an underlying condition (sepsis, obstetrical complications, malignancies, trauma, immune hemolytic transfusion reactions, nephrotic syndrome, others)

Microvascular thrombi block blood flow to vessels and fragment RBCs (schistocytes)

Thrombi consume clotting factors and platelets, activate fibrinolysis, resulting in systemic bleeding

PTT, APTT, TCT are increased; fibrinogen decreased; decreased platelets, increased D-dimers, schistocytes on peripheral blood smear

16

What are the acquired functional platelet abnormalities caused by?

Drugs (common cause): aspirin, others

Uremia, liver disease, cardiopulmonary bypass

Hematological diseases (anemia, myeloproliferative neoplasms, myelodysplastic syndroms, plasma cell myeloma)

17

Bernard Soulier syndrome

An inherited functional platelet abnormality

Adhesion defect due to mutation in GP Ib-IX-V

Thrombocytopenia and giant platelets

Tx: platelet transfusion

18

Glansmann thrombasthenia

An inherited functional platelet abnormality

Aggregation defect due to mutation in GP-IIb-IIIa receptor

PLT count normal

Tx: plasma transfusion

19

Inherited von Willebrand disease

Most common bleeding disorder

Various types; quantitative or qualitative

Most common in O type individuals

Mucocutaneous bleeding

Variable severity

Screening tests: PLT count normal, bleeding time increased, APTT increased or normal (since VWF binds to FVIII and extends its half-life), PTT and TCT normal

20

DDAVP (desmopressin)

Given to increased release of VWF from endothelial cells

Used in treatment of von Willebrand disease

21

Acquired von Willebrand syndrome

Various causes: VWF autoanitbody production, increased proteolysis, decreased production or adsorption to activated cells

Associated w/ myeloproliferative and lymphoproliferative disorders, autoimmune disease, plasma cell dyscrasias

Similar symptoms to inherited VWD by different pt history

May have decreased or functionally defective VWF

22

Hemophilia A

An inherited disorder of secondary hemostasis

Deficiency of factor VIII

X-linked recessive

Anatomical bleeding and hemarthroses

APTT prolonged, PT and TCT normal

Use factor VIII assay to determine activity`

23

Hemophilia B

An inherited disorder of secondary hemostasis

Also called Christmas disease

Deficiency of factor IX

X-linked recessive

Anatomical bleeding and hemarthroses

APTT prolonged, PT and TCT normal

Use factor IX assay to determine activity`

24

Deficiencies of what factors cause no bleeding symptoms?

XII, PK, HK

25

What are causes of acquired disorders of secondary hemostasis?

Coagulation inhibitors
Vitamin K deficiency
Liver disease
Disseminated intravascular coagulation (DIC)

26

What are coagulation inhibitors?

Factor-specific antibodies prevent function of factor; anti-factor VIII most common

Lupus anticoagulant

27

Alloantibody to factor VIII

In pts w/ inherited hemophilia A

Bleeding due to decreased effectiveness of therapeutic factor VIII

28

Autoantibody to factor VIII

In elderly, post-pregnancy, autoimmune disease

Acquired hemophilia A

29

Lupus anticoagulant

Anti-phospholipid antibody

No bleeding symptoms

Increased risk of thrombosis and pregnancy loss

Increased APTT but no bleeding

30

What can be done do determine if inhibitor is causing increased APTT?

Inhibitor if no correction w/ normal plasma in a mixing study

31

Vitamin K deficiency

Causes deficiencies in factors II, VII, IX, X

Prolonged PT and APTT

Normal TCT and fibrinogen level

Only PT prolonged in early deficiency (factor VII has shortest half-life)

32

Liver disease

Multiple coagulation factor deficiencies since liver is site of synthesis of coagulation factors

Prolonged PT, APTT, TCT

Dysfibrinogenemia, increased fibrinolysis, platelets may be decreased or functional

33

What can be done to distinguish liver disease from vitamin K deficiency?

Factor V and VII assays

Both are decreased in liver disease

Only factor VII is decreased in vitamin K deficiency