Bleeding Disorders Flashcards
What are the 4 steps to normal hemostasis (clot formation)?
- Vasoconstriction
- Platelet plug formation
- Coagulation cascade to stabilize clot
- Limit fibrin clot
If there is a primary hemostasis disorder that causes excessive bleeding, how is it likely inherited?
Autosomal Dominant (primary = platelet plug formation)
If there is a secondary hemostasis disorder that causes excessive bleeding, where are the bleeds usually located?
Joints - hemarthroses
4 types of bleeding disorders?
- Vessel wall abnormalities
- Reduced platelet number
- Reduced platelet function
- Clotting factor abnormalities
PT measures?
Extrinsic pathway (tissue factor + FVII)
PTT measures?
Intrinsic pathway
What is an example of a vessel wall abnormality that leads to excessive bleeding in the periorbital region?
Perivascular amyloid in myeloma
= periorbital bruising (raccoon eyes)
< 150K platelets
Thrombocytopenia
Symptoms for thrombocytopenia usually manifest at what number of platelets?
< 50K
Dangerous spontaneous bleeds with thrombocytopenia can occur when the number of platelets is below?
< 20K
What are 3 immune destruction disorders of platelets?
- HIV-associated thrombocytopenia
- Drug-induced thrombocytopenia
- Immune Thrombocytopenic Purpura (ITP)
HIV-associated thrombocytopenia suppresses bone marrow by?
Infecting hematopoietic stem cells
HIV-associated thrombocytopenia will produce _____ against platelets
Autoantibodies
Drug-induced thrombocytopenia via Myelosuppression occurs from?
Chemotherapy, Chloramphenicol and others
Drug-induced immune thrombocytopenia occurs from?
Quinidine, Vancomycin, Heparin
Heparin induced immune thrombocytopenia involves what cascade of events?
PF4 - Heparin complex activates IgG
- IgG binds to the Fc receptor and activates platelets
- Platelets are degraded by IgG
What happens with Immune Thrombocytopenic Purpura (ITP)?
Autoantibodies against platelets bind to platelets
- Macrophages destroy platelets
Acute form of Immune Thrombocytopenic Pupura occurs in?
Kids
Chronic form of immune thrombocytopenic purpura occurs in?
Young adult women
What are the symptoms seen with Immune Thrombocytopenic Purpura?
Petechiae, purpura, thrombocytopenia, platelet antibodies and increased megakaryocytes in marrow
Increased Megakaryocytes in the bone marrow could indicate?
Immune Thrombocytopenic Purpura
Treatment for Immune Thrombocytopenic Purpura?
Corticosteroids
IVIg
CD20 - rituximab
What are 2 Non-immune destruction disorders of platelets?
Thrombotic Thrombocytopenia Purpura (TTP)
Hemolytic Uremic Syndrome
Normally, what metalloproteinase converts multimers of vWF to smaller multimers?
ADAMTS13
In Thrombotic Thrombocytopenic Purpura, what is missing or inhibited?
ADAMTS13
Results of Thrombotic Thrombocytopenic Purpura missing ADAMTS13?
Formation of ultra-large multimers of vWF that initiate aggregation and thrombosis
What is the treatment for Thrombotic Thrombocytopenic Purpura?
Plasma exchange therapy to take out autoantibodies for ADAMTS13 and multimers and give ADAMTS13
What are the 5 main symptoms of Thrombotic Thrombocytopenic Purpura?
Fever Thrombocytopenia MAHA - Microangiopathic Hemolytic Anemia Renal failure Neurologic Defects
What toxin is associated with Hemolytic Uremic Syndrome?
Shiga-like toxin elaborated by E.coli 0157 H7
Patients with Hemolytic Uremic Syndrome present first with?
Bloody diarrhea
Patients with Hemolytic Uremic Syndrome present with what 3 main symptoms?
MAHA
Thrombocytopenia
Renal failure
What is MAHA?
Microangiopathic Hemolytic Anemia
= Platelet aggregation causes passing RBCs to shear and create schistocytes
What 2 platelet destruction disorders involve MAHA?
Thrombotic Thombocytopenic Purpura
Hemolytic Uremic Syndrome
= when platelet aggregation causes passing RBCs to shear and create schistocytes
What are 3 inherited disorders due to defective platelet function?
Bernard - soulier
Glanzmann Thrombasthenia
Storage pool disorders
What are 2 acquired disorders due to defective platelet function?
Aspirin use
Uremia
No adhesion, lack of GP1b
Bernard - Soulier
No aggregation, lack of GP2b3a
Glanzmann Thrombasthenia
No release of dense granules
Storage pool disorders
No release of alpha granules
Grey platelet syndrome
Platelet vs. coagulation disorders - depth of bleed
Platelet = superficial mucosal bleeding Coagulation = deep soft tissue bleeding
Platelet vs. coagulation disorders - petechiae?
Platelet = petechiae present Coagulation = Minimal petechiae
Platelet vs. coagulation disorders - bruise size
Platelet = small, superficial bruises Coagulation = Large, deep bruises
Platelet vs. coagulation disorders - hemarthroses?
Platelet = rare hemarthroses Coagulation = common hemarthroses
Platelet vs. coagulation disorders - time to bleed?
Platelet = bleeding after minor cuts Coagulation = delayed bleeding after cuts
Why is it important for circulating vWF to join factor VIII?
It takes VIII to the site of the platelet plug so that factor VIII can activate the coagulation cascade and further stabilize the clot
vWF disease type 1
Decreased secretion of vWF
vWF disease type 1c
Increased clearance of vWF
vWF disease type 3
SEVERE decreased secretion of vWF
vWF disease type 2
lack of appropriate interaction with ligands
vWF disease type 2a
Lack of multimer assembly
Hemophilia A involves what coagulation factor?
VIII
Hemophilia B involves what coagulation factor?
IX
How are both Hemophilia A and B inherited?
X-linked recessive
Overall summary of Disseminated Intravascular Coagulation?
Coagulation activates
Thrombi form
Everything gets used up
Bleed occurs
With DIC, tissue injury, sepsis and conception products cause what to be release?
Tissue factor
The release of tissue factor causes what with DIC?
Widespread thrombosis
With DIC, widespread thrombosis causes what main things?
- Consumption of platelets and clotting factors
2. Proteolysis of clotting factors
Consumption of platelets and clotting factors with DIC will cause ____ platelets and _____ PT/PTT
Decreased platelets
Increased PT/PTT
Proteolysis of clotting factors with DIC will cause increased?
D-dimer
What is the end result of DIC?
BLEEDING
