Pathology of Red Blood Cells and Bleeding Disorders (Part 3 of 3) Flashcards
What components are involved in primary bleeding disorders?
platelets, vWF, and vessel wall
what components are involved in secondary bleeding disorders?
coagulation
what components are involved in tertiary bleeding disorders?
fibrinolysis factors
what is the timing of bleeding for primary bleeding disorders?
immediate
what is the timing of bleeding for secondary bleeding disorders?
delayed
what is the inheritance pattern for primary bleeding disorders?
autosomal dominant
what is the inheritance pattern for secondary bleeding disorders?
autosomal or x-linked recessive
what is an example of a more extreme vessel wall disorder?
hereditary hemorrhagic telangiectasia
perivascular amyloid is a red flag for what?
myeloma
what is the technical value for thrombocytopenia?
platelet count less than 150,000
when do symptoms of thrombocytopenia typically present?
when platelet count is less than 50,000
when might you get dangerous spontaneous bleeding with thrombocytopenia?
when platelet count is less than 20,000
what could be happening to cause thrombocytopenia?
decreased production, decreased survival, or sequestration
what occurs with HIV-associated thrombocytopenia?
HIV can suppress marrow by infection of HSC or autoantibodies can form against platelets
what could cause myelosuppression?
chemotherapy, chloramphenicol, penicillamine, or gold salts
what could cause drug-induced immune thrombocytopenia?
quinidine, vancomycin, and heparin
What is an example of immunologic destruction of platelets?
immune thrombocytopenic purpura (ITP)
what is immune thrombocytopenic purpura (ITP)?
when antibodies are created against platelets- a sensitized platelet is covered with these opsonizing antibodies and then our own spleen sees the antibody and the splenic macrophages clear them
how does ITP present?
petechiae, purpura, CBC will show thrombocytopenia, platelet antibodies may be present, bone marrow will show increased megakaryocytes
how do you treat ITP?
by reducing the immune response using corticosteroids, IV Ig, and anti-CD20
what is the medication name for anti-CD20?
rituximab
What are two examples non-immunologic destruction of platelets?
thrombotic microangiopathies: 1. thrombotic thrombocytopenic purpura (TTP) 2. hemolytic uremic syndrome (HUS)
what are the symptoms of TTP?
the pentad: fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurologic defects, renal failure
what are the symptoms of HUS?
there is an overlap of symptoms with TTP, but less neuro manifestations and more renal; HUS is more likely to be seen in kids
what occurs during TTP/HUS?
there is an exaggerated platelet plug that is activated- so instead of just a controlled normal platelet plug formation, there is a large inappropriate platelet plug; as you consume these platelets by formation of this platelet plug- thats where the thrombocytopenia is coming in; as these red cells go by, they shear against these little thrombotic foci and as they shear that’s where the actual hemolytic anemia comes from–> forms schistocytes
most cases of TTP are associated with a defect in what?
the metalloproteinases ADAMTS13
what do most patients with TTP respond well to and why?
plasma exchange therapy- because most patients with TTP have the form with the autoantibodies against ADAMTS13
how does plasma exchange therapy work with patients with TTP?
it takes away the multimers and antibodies and provides the patients with ADAMTS
How is HUS different than TTP?
it is still a TMA (thrombotic microangiopathy) but it is not associated with ADAMTS13
what is the most likely etiology of a typical case of HUS?
a shiga-like toxin elaborated by E. coli O157:H7
how does typical HUS caused by shiga-like toxin present?
first with bloody diarrhea, but then when you do further evaluation, you may find the triad of symptoms associated with HUS
what is the HUS triad?
microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal insufficiency
what is the atypical form of HUS linked to?
complement dysfunction
how do you treat HUS?
supportive therapy often leads to full remission
what is the general description of bernard-soulier?
no adhesion
what is the general description of glanzmann thrombasthenia?
no aggregation
what is the general description of storage pool disorders?
there is no granule (ADP/thromboxane) release
what are two examples of acquired forms of defective platelet function?
aspirin use and uremia
what is grey platelet syndrome?
when you don’t have alpha granules in your platelets, you’ll have a bleeding tendency, the platelets are big and gray in appearance and lack granules
von willebrand diseases present more like platelet disorders, but one von willebrand disease will be more like the type of bleeding you get in coagulation disorders. Which type?
type 3
what is the vWF-FVIII complex?
secreted vWF has an important role- it is going to meet up with factor VIII and takes it where it needs to go- onto the surface of the platelet plug
Von willebrand disease is going to fall into 1 of 2 major categories. what are these categories?
quantitative defects and qualitative defects
in what types of von willebrand disease are the quantitative defects seen?
type I and type 3
which type of quantitative von willebrand disease is the most severe?
type 3- there is severely decreased/ absent vWF
what is type 1C von willebrand disease?
vWF is actually created, but it is so unstable that it is rapidly degraded- so there is increased clearance of vWF in type 1C von willebrand disease
in what types of von willebrand disease are the qualitative defects seen?
type 2
how are type 2 von willebrand diseases defined?
a lack of appropriate interaction with ligands
what is the most common type of qualitative von willebrand disease?
type 2A
what occurs in type 2A von willebrand disease?
there is a lack of multimer assembly- so vWF binding to other vWF does not happen with this type
Type 3 von willebrand disease resembles what other disorder?
hemophilia
what is the inheritance pattern of hemophilia?
x-linked recessive
what is the main difference between hemophilia A and hemophilia B?
hemophilia a is lacking FVIII; hemophilia B is lacking FIX
how do you treat hemophilia a? how do you treat hemophilia b?
hemophilia a treatment: replacement factor VIII; hemophilia b treatment: replacement factor IX
what might you have if the labs showed: increased PT, increased PTT, and decreased platelet count?
DIC, liver disease, or lupus
what occurs in DIC?
coagulation activates, thrombi form, everything gets used up, bleeding occurs
what is the common finding in DIC?
there is too much tissue factor being released and tissue factor is a very potent prothrombotic factor
activation of plasmin causes what?
fibrinolysis and proteolysis of clotting factors
what is the syndrome called when the adrenal glands hemorrhage due to DIC?
waterhouse-friderichsen syndrome
with the pathophysiology of DIC, as you are consuming your clotting factors and your platelets, what will you identify?
increased PT/PTT and thrombocytopenia
what does increased d-dimer reflect in a patient with DIC?
reflects the fibrin split products that are occurring from fibrinolysis
Why is bacterial infections not tested in donated blood?
because bacterial sepsis is not going to go unnoticed by the person who has it/ donated the blood
donated blood used for transfusion could cause an infection. What is it?
transfusion transmitted bacterial infection (TTBI)
how does TTBI present and what is it most commonly associated with and why?
dramatic presentation of fever and hypotension during transfusion; mostly associated with platelets because they are stored at room temperature
what is the reaction called when a person with type a blood receives type b blood?
acute immune hemolytic reaction
what antibodies are responsible for the acute immune hemolytic reaction?
preformed IgM antibodies
what is the reaction called when someone with rh negative blood is exposed to rh positive blood?
delayed immune hemolytic response
what antibodies are responsible for the delayed immune hemolytic reaction?
reactive IgG antibodies
what should you suspect if a patient has an anaphylactic reaction while being transfused?
IgA deficiency
what antibodies are responsible for the anaphylactic reaction that occurs in an IgA deficient patient undergoing a transfusion?
IgG
What are two examples of transfusion-related phenomena?
transfusion related acute lung injury (TRALI) and transfusion related immune modulation (TRIM)
How does TRALI present?
acute respiratory failure during or after transfusion; CXR shows diffuse bilateral pulmonary infiltrates; may have a fever and hypotension; may be fatal
what is transfusion related immune modulation?
when there is a pro-inflammatory response and an immune down regulation occurring at the same time
