Ch 20: Hemostatic Disorders

Question 1

Hemostatic vs. Thombotic Disorders

Answer 1

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

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

Question 2

Clinical manifestations of platelet disorder

Answer 2

petechiae and purpuric hemorrhages in the skin and mucous membranes

Question 3

Clinical manifestations of deficiencies of coag factors

Answer 3

hemorrhage in muscles, viscera, and joint spaces

Question 4

clinical manifestation of disorder of blood vessels

Answer 4

purpura

Question 5

senile purpura

Answer 5

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

Question 6

purpura simplex

Answer 6

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

Question 7

scurvy

Answer 7

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

Question 8

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

Answer 8

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

Question 9

Hereditary Hemorrhagic Telangiectasia (Rendu-Osler-Weber Syndrome)

Answer 9

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

Question 10

Allergic purpura (Henoch-Schonlein Purpura)

Answer 10

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

Question 11

Basics of platelet disorders

Answer 11

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).

Question 12

Thrombocytopenia

Answer 12

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

Question 13

May-Hegglin anomaly

Answer 13

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

Question 14

Myosin heavy chain 9 disorders

Answer 14

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)

Question 15

Acute Idiopathic Thrombocytopenia Purpura (ITP)

Answer 15

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

Question 16

Chronic ITP

Answer 16

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

Question 17

Drug-induced autoimmune Thrombocytopenia

Answer 17

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

Question 18

Heparin-Induced Thrombocytopenia

Answer 18

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

Question 19

Pregnancy-Associated Thrombocytopenia

Answer 19

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

Question 20

Wiskott-Aldrich syndrome (WAS)

Answer 20

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

Question 21

X-linked thrombocytopenia

Answer 21

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

Question 22

Fanconi anemia

Answer 22

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

Question 23

Neonatal alloimmune thrombocytopenia (NAIT)

Answer 23

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

Question 24

Posttransfusion purpura

Answer 24

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

Question 25

Thrombotic microangiopathies (TMAs)

Answer 25

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

Question 26

Thrombotic Thrombocytopenia purpura (TTP)

Answer 26

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]

Question 27

Hemolytic-Uremic syndrome (HUS)

Answer 27

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.

Question 28

Hypersplenism

Answer 28

mild thrombocytopenia caused by splenomegaly (of any cause)

Question 29

Kasabach-Merritt Syndrome

Answer 29

consumption of platelets in hemangiomas leadingto thrombocytopenia

Question 30

Bernard-Soulier Syndrome (Giant Platelet Syndrome)

Answer 30

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.

Question 31

Glanzmann Thrombasthenia

Answer 31

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

Question 32

alpha Storage Pool Disease (Grey Platelet Syndrome)

Answer 32

rare inherited disease with no alpha granules. mild

Question 33

delta Storage pool disease

Answer 33

affects dense granules. mild to moderate.

Question 34

acquired qualitative disorders of platelets

Answer 34

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

Question 35

Reactive Thrombocytosis

Answer 35

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

Question 36

Hemophilia A

Answer 36

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.

Question 37

Hemophilia B

Answer 37

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

Question 38

von Willebrand Disease (vWD)

Answer 38

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

Question 39

Type 1 vWD

Answer 39

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

Question 40

Type 2 vWD

Answer 40

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

Question 41

Type 3 vWD

Answer 41

severe. autosomal recessive. vWF activity is absent

Question 42

von Willebrand Factor

Answer 42

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.

Question 43

Liver disease

Answer 43

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

Question 44

Vitamin K deficiency

Answer 44

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.

Question 45

Inhibitors of coag factors

Answer 45

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

Question 46

Bleeding/hemorrhagic “diathesis”

Answer 46

predisposition or tendency

Question 47

DIC pathology

Answer 47

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.

Question 48

DIC causes

Answer 48

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

Question 49

Activated protein C (APC) resistance-factor V Leiden

Answer 49

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

Question 50

Antithrombin deficiency

Answer 50

autosomal dominant w incomplete penetrance. can be quantitative or qualitative

Question 51

Protein S and C deficiencies

Answer 51

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

Question 52

Antiphospholipid Antibody Syndrome

Answer 52

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