Chapter 23: Bleeding disorders Flashcards
What are the general causes of abnormal bleeding?
(1) vascular disorders
(2) Thrombocytopenia
(3) Defective platelet function
(4) Defective coagulation
What is characteristic about vascular and platelet disorders?
Bleeding from mucus membranes and into the skin.
What is characteristic about coagulation disorders?
coagulation disorders tend to bleed into joints and soft tissue.
Are standard screening tests sensitive to bleeding disorders caused by vascular defects?
No because the standard screening tests only test the blood.
What is hereditary vascular telangiectasia?
An uncommon disorder characterized by dilated microvascular swelling throughout the body that can lead to hemorrhage.
How is Hereditary vascular telangiectasia treated?
(1) embolization
(2) laser treatment
(3) estrogens
(4) tranexamic acid
(5) iron supplementation.
Why doe Ehlers-Danlos syndrome lead to bleeding?
Because Ehlers-Danlos syndrome is a congenital abnormality of collagen that leads to defective platelet aggregation.
What does giant cavernous hemangioma lead to?
This disorder leads to DIC.
What bacterial infections are commonly associated with purpura?
Rickettsial infections are commonly associated with purpura.
What is Henoch-Schonlein syndrome?
An IgA mediated vasculitis that commonly follows acute upper respiratory tract infections in children. (Purpuric rash, joint swelling, hematuria)
Why does scurvy lead to bleeding?
Because lack of vitamin C leads to defective collagen which leads to bleeding.
What is steroid purpura?
long term steroid therapy (cushing’s syndrome) can lead to bleeding vis defective vascular support tissue.
What drugs can be used to reduce bleeding by inhibiting fibrinolysis?
Tranexamic acid and aminocaproic acid.
What is the most common cause of thrombocytopenia?
Failure of platelet production
What is chronic idiopathic thrombocytopenic purpura?
It is the most common cause of thrombocytopenic purpura without anemia or neutropenia. Associated with SLE, HIV, CLL, Hodgkin’s disease, hemolytic anemia.
What is the pathogenesis of ITP?
ITP is caused by platelet auto-antibodies that stimulate macrophages to remove platelets from the circulation. GPIIb/IIIa is often the target. Platelet life is reduced from 7-10 days to a few hours.
What are the clinical features of ITP?
(1) insidious onset
(2) easy bruising/bleeding
(3) Mucosal bleeding
How is ITP diagnosed?
(1) platelets are 10,000-50,000
(2) Enlarged platelets
(3) increased megakarycytes
(4) Detection of anti GPIIb/IIIa antibodies.
What are the clinical features of ITP?
(1) insidious onset
(2) easy bruising/bleeding
(3) Mucosal bleeding
What is the goal of ITP treatment?
To keep the platelet count above 50,000
How is ITP diagnosed?
(1) platelets are 10,000-50,000
(2) Enlarged platelets
(3) increased megakarycytes
(4) Detection of anti GPIIb/IIIa antibodies.
What is the goal of ITP treatment?
To keep the platelet count above 50,000
What is the first line treatment for ITP?
Corticosteroids (usually prednisolone)
What are secondary treatments for refractory ITP?
(1) splenectomy
(2) High dose Ig therapy (occupies Fc receptors on macrophages)
(3) Immunosuppressive drugs
(4) Rituximab (anti-CD20)
(5) Stem cell transplant
What is the first line treatment for ITP?
Corticosteroids (usually prednisolone)
What are secondary treatments for refractory ITP?
(1) splenectomy
(2) High dose Ig therapy (occupies Fc receptors on macrophages)
(3) Immunosuppressive drugs
(4) Rituximab (anti-CD20)
(5) Stem cell transplant
What can be done for patients with severe hemorrhaging and ITP?
Platelet transfusions can be a short term solution.
What can be done for patients with severe hemorrhaging and ITP?
Platelet transfusions can be a short term solution.
What is acute ITP?
ITP that occurs in children and is secondary to infections such as chickenpox or infectious mono. It is usually caused by non specific immune complexes.
What is acute ITP?
ITP that occurs in children and is secondary to infections such as chickenpox or infectious mono. It is usually caused by non specific immune complexes.
What drugs can be responsible for drug induced thrombocytopenic purpura?
Quinine, Quinidine, and heparin
What causes familial thrombotic thrombocytopenic purpura?
Mutations to ADAMTS-13 which cleaves vWF polymers. Platelets then adhere to the vWF fibers.
What causes acquired TTP?
(1) infection
(2) AI/connective tissue diseases.
(3) Certain drugs
(4) stem cell transplant
(5) cardiac surgery
What are the five principle features of TTP?
(1) thrombocytopenic purpura
(2) Microangiopathic hemolytic anemia
(3) Neurological abnormalities
(4) renal failure
(5) fever
What causes the microangiopathic hemolytic anemia and thrombocytopenia of TTP?
microvascular thrombosis.
How is TTP treated?
(1) plasma exchange with FFP
(2) cryosupernatant
(3) Rituximab
(4) Immunosuppression
Should platelet transfusions be given in TTP or HUS?
No! platelets are contraindicated (most likely because they would cause further thrombosis.
What is different about HUS in children?
(1) organ damage is limited to kidneys
(2) associated with E. coli and Shigella.
What is disseminated intravascular coagulation?
Thrombocytopenia due the consumption of platelets by inappropriate thrombosis.
Why does splenomegaly cause thrombocytopenia in some cases?
Because the spleen normally sequesters up to 30% of the platelets. However, in splenomegaly up to 90% of the bodies platelets may be sequestered.
What is massive transfusion syndrome?
Platelets do not survive well in stored blood therefore patients that receive many transfusions over a short period may experience thrombocytopenia. FFP or platelet transfusions are necessary.
What signs suggest a disorder of platelet function?
Prolonged bleeding time despite normal thrombocyte counts.
What is Glanzmann’s Thrombasthenia?
An autosomal recessive disorder caused by a mutation to the GPIIb gene.
What is Bernard-Soulier syndrome?
This disorder is characterized by abnormally large platelets and is caused by a mutation to GPIb gene.
What is the defect in grey platelet syndrome?
There is almost a complete absence of alpha granules
What is the defect in beta-storage pool disease?
There is a deficiency of dense granules
What is the defect in vWF disease?
Obviously von Willebrand factor is defective.
What is the most common cause of defective platelet function?
Aspirin is the most common cause of defective platelet function. It inhibits TXA2 production by Cyclooxygenase
How does Dipyridamole inhibit platelet function?
Dipyridamole inhibits platelet function by blocking reuptake of adenosine.
How does Clopidogrel inhibit platelet function?
Clopidogrel inhibits the binding of ADP to its receptor on platelets. It is used for the prevention of thrombotic events.
What are the agents Abciximab, epitifbatide, and triofiban used for?
These agents block the receptor sites of GPIIb/IIIa. They are used for patients with coronary syndromes
What is the effect of hyperglobulinemia on clotting?
Hyperglobulinemia inhibits platelet adherence and aggregation.
What should a physician do initially when investigating a patient with a suspected blood abnormality?
A blood count and a blood film should be the first steps. A bone marrow biopsy may also be necessary.
If a patient has thrombocytopenia, normal or excessive numbers of megakaryocytes and no other abnormalities what is the usual diagnosis?
ITP
When should platelet transfusions be administered?
Platelet transfusions are necessary in thrombocytopenia or impaired platelet function before invasive procedures and during bleeding.
(1) platelets should be kept above 50,000 for surgery and above 20,000 at other times
(2) platelet transfusion should always be seriously considered if platelets fall below 10,000.
