RBCs 2 Flashcards
Mammalian coagulation systems are based primarily upon what enzymes
serine proteases
a coagulopathy result in what
either bleeding or clotting or both
The primary pathway for the initiation of coagulation is what?
the tissue factor (extrinsic) pathway
What test measures intrinsic pathway?
extrinsic?
PTT
PT
PTT measures what molecule?
PT?
heparin
coumadin/warfarin
Abnormal platelet counts are best confirmed by inspection of what?
A peripheral blood smear
a calculation based on PT and is generally utilized to monitor individuals who are being treated with the (oral) anticoagulant warfarin (coumadin)
INR
DIC: PT?
PTT?
bleeding time?
Platelet count?
- long
- long
- long
- decreased
Von Willebrand disease: PT?
PTT?
bleeding time?
Platelet count?
- unaffected
- long or unaffected
- long
- unaffected
Hemophilia: PT?
PTT?
Bleeding time?
Platelet count?
- Unaffected
- long
- unaffected
- unaffected
PT and PTT in uremia
unaffected
PT and PTT in Factor V deficiency
long
How do bleeding disorders caused by vessel wall abnormalities usually present?
- do not usually cause serious bleeding problems
- most often they present with small hemorrhages (petechiae and purpura) in the skin or mucous membranes, particularly the gingivae
Platelet count and test of coagulation (PT and PTT) in bleeding disorders caused by vessel wall abnormalities
usually normal
These are associated with microvascular bleeding that results from collagen defects that weaken vessel walls
Scurvy and Ehlers-Danlos syndrome
Protein wasting effects of excessive corticosteroid production cause loss of perivascular supporting tissue
Cushing syndrome
Systemic IgA deficiency that in the kidney causes a mesangial glomerulonephritis
Henoch-Schonlein purpura
Henoch-Schonlein purpura is characterized by what?
a purpuric rash especially in buttocks and abdomen, colicky abdominal pain, polyarthralgia, and acute glomerulonephritis
An autosomal dominant disorder that can be caused by mutations in at least five different genes, most of which modulate TGF-B
Hereditary hemorrhagic telangiectasia, also know as Weber-Osler-Rendu syndrome
What is Hereditary hemorrhagic telangiectasia characterized by?
dilated, tortuous blood vessels with thin walls that bleed readily. Bleeding can occur anywhere, but it is most common under the mucous membranes of the nose (epistaxis), tongue, mouth and eyes, and throughout the GI tract
A platelet count less than what constitutes as thrombocytopenia
less than 100,000
Platelet counts in what range may aggravate post traumatic bleeding
20-50k
Platelets less than what can be associated with spontaneous (nontraumatic) bleeding? . .petichial and cutaneous
less than 20k
bleeding from thrombocytopenia has what kind of PT and PTT
normal
What is a potential complication of any patient with a markedly decreased platelet count and is the most feared complication
intracranial bleeding
What are the 4 categories of causes of thrombocytopenia?
- Decreased platelet production
- Decreased platelet survival
- Sequestration
- Dilution
caused by autoantibody mediated destruction of platelets
Chronic immune thrombocytopenic purpura (ITP)
The thrombocytopenia of chronic ITP is usually markedly imporoved by what?
splenectomy
Chronic ITP: spleen size?
Marrow?
Peripheral blood?
- normal
- modestly increased number of megakaryocytes
- abnormally Large platelets (megathrombocytes) which are a sign of accelerated thrombopoiesis
Age and gender for ITP
adult women under 40
Chronic ITP is characterized by what?
- -bleeding into the skin and mucosal surfaces
- cutaneous bleeding is seen in the form of pinpoint hemorrhages which are especially prominent in dependent areas where capillary pressure is higher
- petechiae can become confluenet giving rise to ecchymoses
- history of easy bruising, nosebleeds, bleeding from gums, and hemorrhages into soft tissue from minor trauma
- may manifest first with melena, hemoturia, or excessive menstrual flow
- subarachnoid hemorrhage and intracerebral hemorrhage are serious and sometimes fatal complications
splenomegaly and lymphadenopathy in chronic primary ITP
uncommon . . . their presence should lead one to consider other diagnosis such as ITP secondary to a B cell neoplasm
ACUTE ITP is mainly a disease of what age?
After what?
- a disease of childhood equally in both sexes
- symptoms appear abruptly often 1 to 2 weeks after a self limited viral illnes
Resolution of Acute ITP?
self-limited usually resolving spontenously within 6 months . .Glucocorticoids are given only if the thrombocytopenia is severe
What are the most common drugs implicated in drug induced thrombocytopenia
- Quinine
- Quinidine
- Vancomycin
Describe the 2 types of HIT
- Type I: rapidly after initiation of therapy. Generally resolves and typically is of little clinical importance
- Type II: less common, more clnically important. Begins 5-14 days after initiation of therapy. Results in severe, sometimes life threatening venous and arterial thrombosis, despite the thrombocytopenia
What is one of the most common hematologic manifestations of HIV infection
thrombocytopenia
contrast TTP and HUS to DIC
IN TTP and HUS, activation of the coagulation cascade is not of primary importance, and hence laboratory assessments of coagulation such as PT and PTT are usually normal
cause of typical HUS
E. coli 0157:H7
What causes atypical HUS
-alternative complement pathway inhibitor deficiencies (complement factor H, membrane cofactor protein (CD46), or factor I . . especially during pregnancy
deficiency is ADAMTS13
TTP: thrombotic thrombocytopenic purpura
What does ADAMTS13 normally do?
normally degrades very high molecular weight multimers of von Willebrand factor (vWF). In its absence they can accumulate in plasma and tend to promote platelet activation and aggregation
Inherited disorders of platelet function can be classified into 3 pathogenically distinct groups
- defects of adhesion
- defects of aggregation
- disorders of platelet secretion
inherited deficiency of the platelet membrane glycoprotein complex ib-IX. This glycoprotein is a receptor for vWF and is essential for normal platelet ADHESION to the subendothelial ECM
Bernard-Soulier syndrome
autosomal recessive defect of platelet aggregation due to deficiency or dysfunction of glycoprotein IIb-IIIa
Glanzmann thrombasthenia
The most common and important INHERITED deficiency of coagulation factors affect what factors? called what?
- VIII (hemophilia A)
- IX (hemophilia B)
A deficiency in this influences both coagulation and platelet function
vWF
ACQUIRED deficiencies of coagulation factors usually involve ____
multiple
vitamin K deficiency results in the impaired synthesis of which factors
II, VII, IX, X
What is the most common inherited bleeding disorder
Von Willebrand disease
What types of Von Willebrand Disease exhibit quantitative defects in vWF?
Qualitative?
I and III
II
Which type of Von Willebrand Disease has very low levels of vWF and has severe clinical manifestations that may resemble hemophilia
Type III
What measures the plasma level of active vWF
ristocetin cofactor activity . . reduced in Von Willebrand disease
Because vWF stabilizes factor VIII, a deficiency in vWF gives rise to a secondary decrease in factor VIII levels, reflected as what?
increased PTT in types 1 and 3
Persons with von Willebrand disease facing hemostatic challenges like dental work or surgery can be treated with what?
desmopressin which stimulates vWF release, or with infusions of plasma concentrates containing factor VIII and vWF
What is the most common hereditary disease associated with life threatening bleeding
Hemophilia A
inheritance of hemophilia A
X linked recessive . .affects mainly males and homozygous females
clinical features of Hemophilia A
- easy bruising and massive hemorrhage
- hemarthroses
- petechiae ABSENT
- Prolonged PTT
- normal PT
What particular sites do hemophiliacs tend to bleed
joints, muscles, CNS
how is hemophilia A treated
infusions of recombinant factor VIII
What is the crippling effect of repeated bleeds into a joint seen in hemophilia A
- loss of range of motion
- muscle loss
- destruction of joints themselves
Other names for Hemophilia B
- Christmas Disease
- Factor IX deficiency
Hemophilia A vs. B clinically
indistinguishable
What can you look for with DIC
fibrin split products
What are the two major mechanisms that trigger DIC?
- release of tissue factor, or other poorly characterized procoagulants into circulation
- widespread injury to endothelial cells
About 50% of DIC patients are what?
obstetric pts having complications of pregnancy and the disorder tends to be reversible with delivery of the fetus
What is acute DIC associated with
obstetric complications or major trauma for example is dominated by a BLEEDING diathesis
What is chronic DIC associated with
cancer patients . . tends to present with thrombotic complication
describe most of the complications of transfusion
minor or transient
What is the most common complication of Transfusion?
Describe it
- febrile nonhemolytic reaction
- takes form of fever and chills, sometimes with mild dyspnea, within 6 hours of a transfusion of red cells or platelets
- thought to be caused by inflammatory mediators derived from donor leukocytes
- Symptoms respond to antipyretics and are short lived
Severe, potentially fatal allergic reactions may occur when blood products containing certain antigens are given to previously sensitized recipients. These are most likely to occur in what patients?
- IgA deficiency
- IgG antibodies recognize IgA in the infused blood
This transfusion reaction may be triggered by the presence of an allergen in the donated blood that is recognized by IgE antibodies in the recipient
Urticarial allergic reactions
describe the Urticarial allergic reactions
generally mild . . most respond to antihistamines and do not require discontinuation of the tranfusion
These are usually caused by preformed IgM antibodies against donor red cells that fix complement
Acute hemolytic reactions . . ABO incompatibility
Direct Coombs test with Acute hemolytic reactions
positive
clinical symptoms of acute hemolytic reactions to transfusion
Fever, shaking chills, and flank pain appear rapidly
Reaction caused by IgG antibodies to foreign protein antigens and are associated with a positive direct Coombs test and lab features of hemolysis (low haptoglobin and elevated LDH)
Delayed hemolytic reactions
in a delayed hemolytic reaction to transfusion, antibodies to what often induce sufficient complement activation to cause severe and potentially fatal reactions identical to those resulting from ABO mismatches
Rh, Kell, Kidd
A severe, frequently fatal complication in which factors in a transfused blood product trigger the activation of neutrophils in the lung microvasculature
TRALI: transfusion-related Actue Lung Injury
By far, the most common antibodies associated with TRALI are those that bind what? found in what people?
- MHC
- particularly MHC class I that are often found in multiparous women
TRALI is most likely to occur with products containing high levels of donor antibodies such as what?
fresh frozen plasma and platelets
What is the clinical presentation of TRALI
- dramatic with sudden onset respiratory failure during or soon after a transfusion
- Diffuse bilateral pulmonary infiltrates that do not respond to diuretics are seen on chest imaging
- other associated findings include fever, hypotension, and hypoxemia
Significant bacterial contamination in a transfusion is much more common in what preparations?
platelets rather than red cell preparations due in large part to the fact that platelets must be stored at room temp
