Ch 20: Hemostatic Disorders Flashcards Preview

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Flashcards in Ch 20: Hemostatic Disorders Deck (52):
1

Hemostatic vs. Thombotic Disorders

hemostatic = failure to restore the integrity of an injured vessel (bleeding)

thrombotic = inability to maintain the fluidity of blood (thrombosis)

2

Clinical manifestations of platelet disorder

petechiae and purpuric hemorrhages in the skin and mucous membranes

3

Clinical manifestations of deficiencies of coag factors

hemorrhage in muscles, viscera, and joint spaces

4

clinical manifestation of disorder of blood vessels

purpura

5

senile purpura

superficial age-related atrophy of supportive connective tissue. sharply demarcated purpura on sun-exposed skin. (extravascular)

6

purpura simplex

deep-tissue purpura that usually occurs during menses. (extravascular)

7

scurvy

collagen synthesis disturbance during vitamin c deficiency. exhibits purpura & perifollicular hemorrhages. (extravascular)

8

Causes of immunoglobulin fragments to be deposited in vessel walls, & outcome

amyloidosis, cryoglobulinemia and other paraproteinemias. results in vessel wall weakness and purpura.

9

Hereditary Hemorrhagic Telangiectasia (Rendu-Osler-Weber Syndrome)

autosomal dominant disorder of venules and capillaries which shows arteriovenous malformations of solid organs and telangiectases of mucous membranes and dermis. results in telangiectasias (tortuous, dilated vessels). caused by mutations in TGF-Beta, endoglin (ENG), or ALK1. Recurrent bleeding such as epistaxis and GI hemorrhage limits physical activity

10

Allergic purpura (Henoch-Schonlein Purpura)

vacular disease resulting from immunologic damage to blood vessel walls, characterized by leukocytoclastic vasculitis. Often associated with urticarial lesions, and can involve GI and renal systems

11

Basics of platelet disorders

Represent 1) decreased production, 2) increased destruction, or 3) impaired function. May show history of bleeding disorder, mucocutaneous bleeding, or life-threatening bleeds. Petechiae (nonblanching red lesions < 2mm) which usually occur in lower extremities, buccal mucosa, and at pressure points (e.g. waistband).

12

Thrombocytopenia

Platelet count < 150,000/uL. Can result in spontaneous bleeding, prolonged bleeding time, but normal PT and PTT.

13

May-Hegglin anomaly

congenital decreased production in platelets. most common of the myosin heavy chain 9 disorders.

14

Myosin heavy chain 9 disorders

mutation in MYH9 gene which encodes nonmuscle myosin heavy chain NMMHC-IIA. Includes May-Hegglin, Epstein, Fechtner, and Sebastian platelet syndromes. Abnormal megakaryocytopoeisis leads to macrothrombocytopenia (large platelets) and abnormal neutrophils with Dohle-like bodies (blue cytoplasmic inclusions)

15

Acute Idiopathic Thrombocytopenia Purpura (ITP)

typically in children after virus, which can change platelet antigens, eliciting autoantibodies. platelet count reaches < 20,000. characterized by sudden onset of petechiae and purpura

16

Chronic ITP

immune thrombocytopenic purpura that most frequently occurs in adult women. associted with collagen vascular diseases, lymphoproliferative disease, and HIV. Depends on levels of autoantibodies, degree of inhibition of megakaryocytes, and expression of Fc and complement receptors on macrophages. manifests as sudden bleeding episodes

17

Drug-induced autoimmune Thrombocytopenia

many drugs complex with platelets to create a neotope that attracts autoantibodies.

18

Heparin-Induced Thrombocytopenia

(HIT) Type 1 = mild, self limited aggregation. Type 2 = acquired IgG against platelet factor 4-heparin complexes. Hypercoagulable state, can be lethal

19

Pregnancy-Associated Thrombocytopenia

3rd trimester- platelets become diluted. Can be result of (pre)eclampsia and HELLP (Hemolysis, Elevted Liver enzyme tests and Low Platelets)

20

Wiskott-Aldrich syndrome (WAS)

x-linked recessive disorder in WASP gene, causing small platelets, eczema, and immunodeficiency

21

X-linked thrombocytopenia

defets in WASP gene, but only exhibits thrombocytopenia, not the other symptoms of WAS

22

Fanconi anemia

autosomal recessive bone marrow failure manifesting as thrombocytopenia and RBC macrocytosis due to mutation in a family of genes involved in DNA repair. Many congenital anomalies associated

23

Neonatal alloimmune thrombocytopenia (NAIT)

alloimmunization resulting from HPA-1a-negative mother's Ig's against paternal HPA-1a-positive antigens on fetal platelets.

24

Posttransfusion purpura

Can develop in people who are HPA-1 negative who have developed antibodies to either due to pregnancy or previous transfusions.

25

Thrombotic microangiopathies (TMAs)

heterogenous group os syndromes (including TTP and hemolytic uremic sundrome) with common features including thrombocytopenia, microangiopathic hemolytic anemia, meuro symptoms, fever, and renal impairment

26

Thrombotic Thrombocytopenia purpura (TTP)

Probably results from platelet aggregating substance(s) being introduced to crculation, possibly inappropriate vWF multimers from injured endothelium that cross-links platelets. ADAMTS13 metalloprotease is deficient and doesn't cleave lage multimers. Pathologic hallmark is deposition of PAS-positive hyaline microthrombi in arterioles and capillaries. Schistocytes present. Most common in women in 30s and 40s and often fatal. Widespread purpura, anemia, and neuro symptoms. Distinguished from DIC by normal PT, PTT, and [fibrinogen]

27

Hemolytic-Uremic syndrome (HUS)

Resembles TTP, but usually in children adter hemmorhagic e coli O157:H7 or Shigella. Shiga-like toxin actiaates platelets causing fibrinogen to bind to Gp IIb/IIIa complex and platelet aggregation. Kidney failure is the main clinical feature.

28

Hypersplenism

mild thrombocytopenia caused by splenomegaly (of any cause)

29

Kasabach-Merritt Syndrome

consumption of platelets in hemangiomas leadingto thrombocytopenia

30

Bernard-Soulier Syndrome (Giant Platelet Syndrome)

autosomal recessive exhibiting a quantitave or qualitative defect in platelet membrane complex (Gp Ib/IX and sometimes Gp V) that helps bind vWF. Dx: thrombocytopenia and giant platelets on smear.

31

Glanzmann Thrombasthenia

autosomal recessive caused by quantitative or qualitative defect in Gp IIb/IIIa complex, a receptor for fibrinogen and vWF, leading to decreased platelet aggregation.

32

alpha Storage Pool Disease (Grey Platelet Syndrome)

rare inherited disease with no alpha granules. mild

33

delta Storage pool disease

affects dense granules. mild to moderate.

34

acquired qualitative disorders of platelets

Drugs (COX inhibitors- aspirin is irreversible, antibiotics), renal failure, cardiopulmonary bypass (during surgery), hematologic malignancies (MDS, chronic disorders)

35

Reactive Thrombocytosis

Associated with 1) Fe deficient anemia, 2) splenectomy, 3) cancer, 4) chronic inflammation. Rarely symptomatic

36

Hemophilia A

X-linked Factor VIII deficiency. Mild to severe bleeding, in relation to F VIII levels. can be spontaneous if severe. Degenerative joint disease due to frequent bleeding into joints.Treat w/ factor VIII. HIV infection from transfusions was a problem in the 80s.

37

Hemophilia B

x-linked factor IX deficiency. similar characeristics as Hemphilia A. Factor IX is vitamin K-dependent protein made in liver

38

von Willebrand Disease (vWD)

20 subtypes broken into 3 groups. vWD = autosomal. Mild, except type 3. Unlike hemophilia, pt's experience immediate mucocutaneous bleeding. some hemarthroses. DDAVP = treatment of choice

39

Type 1 vWD

75% of all vWD. Autosomal dominant quantitative deficiency of all multimers of vWF

40

Type 2 vWD

20% of vWD. qualitative defects = defective binding to vessel wall. Type IIa = high molec weight multimers are absent. Type IIb = vWF with increased affinity for platelets leading to potential thrombocytopenia

41

Type 3 vWD

severe. autosomal recessive. vWF activity is absent

42

von Willebrand Factor

vWF is adhesive molecule produced by megakaryocytes and endothelial cells. Polymerizes into multimers and is stored in Weibel-Palade bodies of endotheliial cells. Binds to platelet Gp Ib/IX or CD42 promoting platelet adhesion. Can also bind GP IIb/IIIa (CD41/61) to promote platelet aggregation. In plasma binds and protects factor VIII.

43

Liver disease

Affects the many coag factors which are produced there. Unlike DIC, PT is much more prolonged than PTT because of vitamin-K dependent enzymes are disproportionally affected

44

Vitamin K deficiency

Liver-derived factors (except V) require vitamin K to gamma-carboxylate them to create Gla residues. Affects II, VII, IX, X. Often a result of diet, antibiotics, and colonic resection.

45

Inhibitors of coag factors

Usually IgG autoantibodies against Factor VIII and vWF. Acquired, such as against transfusion elements

46

Bleeding/hemorrhagic "diathesis"

predisposition or tendency

47

DIC pathology

TF expression & Factor VII/platelet activation with substantial amounts of thrombin and inability to neutralize it. Clotting factors, platelets, and fibrinogen are consumed, leading to bleeding. Fibrin split products are anticoagulant, causing more bleeding. Fibrin microthrombi occlude vessels causing ischemia and hemolytic anemia. Azotemia is a symptom of mild renal consequences.

48

DIC causes

complication of massive trauma, burns, cancer, liver disease, OB emergencies, acidosis, hypoxia, shock, immune complex deposition, surgery, hypotension, vasculitis.Endotoxin causes macrophages to release TF. Certain cancer cells release TF. TNF in gram-neg sepsis, viral/rickettsial infection, trauma, and cytokines all damage endothelium

49

Activated protein C (APC) resistance-factor V Leiden

point mutation in F V gene makes it resistant to APC inhibition. Most common cause of thrombosis, especially in whites.

50

Antithrombin deficiency

autosomal dominant w incomplete penetrance. can be quantitative or qualitative

51

Protein S and C deficiencies

C deficient= life-threatening neonatal thrombosis with purpura fulminans. Clinically similar to ATIII deficiency

52

Antiphospholipid Antibody Syndrome

Ig's against several negatively charged protein/lipid complexes, such as phosphatidylserine (PS) and cardiolipin (which are exposed when platelets are activated). Features 1) arterial & venous thrombosis 2) spontaneous abortion 3)immune-mediated thrombocytopenia or anemia. Lupus anticoagulants (which are not restricted to SLE) are antibodies that prolong PTT in vitro but are thrombotic in these patients. Leading acquired hematologic cause of thrombosis