Flashcards in Ch 20: Hemostatic Disorders Deck (52):
Hemostatic vs. Thombotic Disorders
hemostatic = failure to restore the integrity of an injured vessel (bleeding)
thrombotic = inability to maintain the fluidity of blood (thrombosis)
Clinical manifestations of platelet disorder
petechiae and purpuric hemorrhages in the skin and mucous membranes
Clinical manifestations of deficiencies of coag factors
hemorrhage in muscles, viscera, and joint spaces
clinical manifestation of disorder of blood vessels
superficial age-related atrophy of supportive connective tissue. sharply demarcated purpura on sun-exposed skin. (extravascular)
deep-tissue purpura that usually occurs during menses. (extravascular)
collagen synthesis disturbance during vitamin c deficiency. exhibits purpura & perifollicular hemorrhages. (extravascular)
Causes of immunoglobulin fragments to be deposited in vessel walls, & outcome
amyloidosis, cryoglobulinemia and other paraproteinemias. results in vessel wall weakness and purpura.
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
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
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).
Platelet count < 150,000/uL. Can result in spontaneous bleeding, prolonged bleeding time, but normal PT and PTT.
congenital decreased production in platelets. most common of the myosin heavy chain 9 disorders.
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)
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
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
Drug-induced autoimmune Thrombocytopenia
many drugs complex with platelets to create a neotope that attracts autoantibodies.
(HIT) Type 1 = mild, self limited aggregation. Type 2 = acquired IgG against platelet factor 4-heparin complexes. Hypercoagulable state, can be lethal
3rd trimester- platelets become diluted. Can be result of (pre)eclampsia and HELLP (Hemolysis, Elevted Liver enzyme tests and Low Platelets)
Wiskott-Aldrich syndrome (WAS)
x-linked recessive disorder in WASP gene, causing small platelets, eczema, and immunodeficiency
defets in WASP gene, but only exhibits thrombocytopenia, not the other symptoms of WAS
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
Neonatal alloimmune thrombocytopenia (NAIT)
alloimmunization resulting from HPA-1a-negative mother's Ig's against paternal HPA-1a-positive antigens on fetal platelets.
Can develop in people who are HPA-1 negative who have developed antibodies to either due to pregnancy or previous transfusions.
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
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]
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.
mild thrombocytopenia caused by splenomegaly (of any cause)
consumption of platelets in hemangiomas leadingto thrombocytopenia
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.
autosomal recessive caused by quantitative or qualitative defect in Gp IIb/IIIa complex, a receptor for fibrinogen and vWF, leading to decreased platelet aggregation.
alpha Storage Pool Disease (Grey Platelet Syndrome)
rare inherited disease with no alpha granules. mild
delta Storage pool disease
affects dense granules. mild to moderate.
acquired qualitative disorders of platelets
Drugs (COX inhibitors- aspirin is irreversible, antibiotics), renal failure, cardiopulmonary bypass (during surgery), hematologic malignancies (MDS, chronic disorders)
Associated with 1) Fe deficient anemia, 2) splenectomy, 3) cancer, 4) chronic inflammation. Rarely symptomatic
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.
x-linked factor IX deficiency. similar characeristics as Hemphilia A. Factor IX is vitamin K-dependent protein made in liver
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
Type 1 vWD
75% of all vWD. Autosomal dominant quantitative deficiency of all multimers of vWF
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
Type 3 vWD
severe. autosomal recessive. vWF activity is absent
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.
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
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.
Inhibitors of coag factors
Usually IgG autoantibodies against Factor VIII and vWF. Acquired, such as against transfusion elements
predisposition or tendency
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.
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
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.
autosomal dominant w incomplete penetrance. can be quantitative or qualitative
Protein S and C deficiencies
C deficient= life-threatening neonatal thrombosis with purpura fulminans. Clinically similar to ATIII deficiency