Platelets disorder FA USMLERx flash crds p.397 Mar 30 16
What will the platelets in Bernard-Soulier Syndrome look like?
Abnormally large platelets
At the platelets Where are the proteins found? How many are they Which one is the most important How do they work
Numerous proteins on the surface of platelets help platelets work properly. One type of these proteins is called GLYCOPROTEIN. Various glycoproteins are found on the platelet surface and work together like A BRIDGE TO CONNECT PLATELETS with each other and to the wall of the injured blood vessel
What are glycoproteins found on the platelet
Numerous proteins on the surface of platelets help platelets work properly. One type of these proteins is called glycoprotein. Various glycoproteins are found on the platelet surface
How do the glycoproteins work Step I adhesion Step II adhesion/activation
Various glycoproteins work together like a bridge to Connect platelets with each other and to The wall of the injured blood vessel
A patient with purpura and menorrhagia Has low platelets. Antiplatelet antibodies are found. What can trigger this condition?
Viral illnesses may trigger it this is immune thrombocytopenia IT involving decreased platelet survival and increased marrow megakaryocytes) Most children with ITP, the disorder follows a viral illness ... Chickenpox, mumps, rubella, Epstein-Barr virus, or parvovirus
The importance of Weibel-Palade bodies in the endothelia cells
Weibel-Palade bodies (WPB) are the regulated secretory organelles of endothelial secrete proteins vWF; von Willebrand disease.
What is the mechanism by which Bernard-Soulier Syndrome causes a defect in the interaction of platelets? What causes Bernard-Soulier Syndrome?
A decrease in the molecule GLYCOPROTEIN IB leads to a defect in binding Platelet-to-vWF adhesion so Platelets Will not be able to bind to vWF and forming the platelet plugs, Autosomal recessive. Decrease in GpIb leads to a defect in platelet plug formation. Platelets will not be able to bind to vWF.
What enzyme is deficient in patients with thrombotic thrombocytopenic purpura TTP?
ADAMNT13 enzyme von Willebrand factor released from Weibel-Palade bodies ADAMTS 13 is a metalloprotease that degrades von Willebrand factor multimers released by Also known as VON WILLEBRAND FACTOR-CLEAVING PROTEASE VWFCP A lack of activity of the ADAMTS13 enzyme-protein in the blood causes TTP Thrombotic Thrombocytopenic Purpura
Short For A Disintegrin And Metalloproteinase
A. D. A. M.TS. 13 A-A D-Disintegrin A-And M-Metalloproteinase T-Thrombospondin 13-13 member
What is the antibody target in Immune thrombocytopenia? What is characteristically Elevated on bone marrow biopsy?
Antibodies against glycoprotein IIb/IIIa causing platelet-antibody complex destruction by splenic macrophages; megakaryocytic are elevated MEGAKARYOCYTIC "large-nucleus cell" in bone marrow cell with a lobulated nucleus responsible for the production of blood thrombocytes platelets, which are necessary for normal blood clotting. ( Remarque that the glycoproteins glycoprotein IIb/IIIa are the same seen in Glanzmann thrombasthenia )
What happen at the RBC when the Hb is denatured How is bite cell forming
BITE CELLS RBC "bite cell" is an abnormally shaped RBC with one or more semicircular portions removed from the cell margin. These "bites" result from the removal of denatured hemoglobin by macrophages in the spleen. e.g. Glucose-6-phosphate dehydrogenase deficiency, in which uncontrolled oxidative stress causes HEMOGLOBIN TO DENATURE AND FORM HEINZ BODIES, is a common disorder that leads to the formation of bite cells. Bite cells can contain more than one "bite." Glucose 6-PD deficiency SECONDARY TO chemical poisoning or injury by oxidant drugs are settings for HEINZ BODY FORMATION
How will a ristocetin cofactor assay differentiate between Bernard-Soulier syndrome and Glanzmann thrombasthenia?
Bernard-Soulier syndrome will not have agglutination on ristocetin cofactor assay, whereas Glanzmann thrombasthenia will have agglutination
What coagulation test will indicate a problem with platelet function?
Bleeding time for platelets-vessel interaction
A patient has petechiae and recurrent epistaxis. Blood smear shows no platelet clumping. What will bleeding time and platelet count show?
Bleeding time is increased and platelet count is normal This is Glanzmann thrombasthenia Poor platelet-to-platelet aggregation in platelet plug formation due to decreased glycoprotein IIb/IIIa
A patient has petechiae and recurrent epistaxis. Blood smear shows no platelet clumping. What will bleeding time and platelet count show?
Bleeding time is increased and platelet count is normal (this is Glanzmann thrombasthenia)
Difference b/w Bleeding into a third space- internal organs or Bleeding from capillaries
CAPILLARY BLEEDING from Skin Subcutaneous tissue or Mucous membranes Exempli gratia-given e.g BERNARD-SOULIER DZ Glanzmann's Thrombasthenia THIRD SPACE BLEEDING Forming Hematoma After surgery Trauma, joins, head. internal organs or Third Space Coagulation factor defect exempli gratia (e.g) example given HEMOPHILIA A
What will the platelet count and bleeding time look like in Bernard-Soulier Syndrome?
Decreased platelet count and increased bleeding time. Bernard-Soulier syndrome (BSS) is hereditary platelet disorders characterized by Thrombocytopenia, Giant platelets, and a Tendency toward Bleeding
What is the treatment for Bernard-Soulier Syndrome?
Desmopressin and platelet transfusion
Hemophilia - The "Royal Disease"
Hemophilia Types A and B Hemophilia stems from a genetic defect inherited Recessively on the X Chromosome. This explains the fact that there are more male than female patients affected as the defect in females can be cancelled out by the presence of a second X chromosome in female genes.
A patient has bleeding from the gums, epistaxis, petechiae, and purpura. What is the likely defect in coagulation?
Increased bleeding time with or without a platelet count reduction these describe the microhemorrhages capillaries associated with platelet disorders
What happen if ADAMS 13 can not cutThe largest multimers in blood
Platelets form a clot
Glanzmann thrombasthenia causes a defect in what aspect of platelet interaction
Poor platelet-to-platelet aggregation in platelet plug formation due to decreased glycoprotein IIb/IIIa Glanzmann thrombasthenia (GT) is a rare genetic platelet disorder in which the platelets have qualitative or quantitative deficiencies of the fibrinogen receptor αIIbβ3. The αIIbβ3 receptors adherence to platelets to the endothelium in platelet aggregation. The αIIbβ3 complex binds fibrinogen and/or von Willebrand factor (vWF). Adjacent platelets are cross-linked through the αIIβ3. When the complex functions abnormally, platelets cannot aggregate. This then leads to increased bleeding.
Why the antibiotic Ristocetin is no longer used Why is ristocetin used in vitro What dz. can be differentiated
Ristocetin is an antibiotic, previously used to treat staphylococcal infections. It is no longer used clinically because It caused thrombocytopenia and platelet agglutination. It is now used solely to assay functions in vitro in the diagnosis of von Willebrand disease (vWD) and Bernard-Soulier syndrome and they will not have agglutination Bernard-Soulier syndrome is a severe bleeding disease due to a defect of GPIb/IX/V, a platelet complex that binds the von Willebrand factor Platelet agglutination caused by ristocetin can occur only in the presence of von Willebrand factor multimers and the GPIb/IX/V platelet complex binds the von Willebrand factor So if ristocetin is added to blood lacking the Willebrand factor THE PLATELETS COMPLEX WILL NOT CLUMP WILL NOT HAVE AGGLUTINATION The antibiotic ristocetin causes von Willebrand factor to bind the platelet receptor glycoprotein Ib (GpIb), so when ristocetin is added to normal blood, it causes agglutination.
Schistocytes vs. bite cells Where are they seen ?
SCHISTOCYTES is seen in TTP are a general term for a FRAGMENTED RED BLOOD CELL that may assume various shapes Horn-like projections (keratocytes) Triangle-forms (triangulocytes) Helmet shapes. SCHISTOCYTES ARE formed WHEN erythrocytes are forced through a Vessel blocked with interlacing fibrin strands and the RBCs ARE SLICED INTO FRAGMENTS. These damaged cells continue to circulate while healing their Torn edges. Heinz bodies is seen in G6P defect Heinz bodies are inclusions within red blood cells composed of denatured hemoglobin RBC"Bites" result from the removal of denatured hemoglobin by macrophages in the spleen.
What does ADAMS stand for? What is the relationship with TTP
Short For A Disintegrin And Metalloproteinase A. D. A. MTS. 13 (A Disintegrin And Metalloproteinase with a thrombospondin type 1 motif, member 13 —also known as VON WILLEBRAND FACTOR-CLEAVING PROTEASE (VWFCP) —is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is secreted in blood and degrades large vWf multimers, decreasing vWf multimers activity. A lack of activity in the ADAMTS13 enzyme (a type of protein in the blood) CAUSES (TTP) THROMBOTIC THROMBOCYTOPENIC PURPURA The ADAMTS13 gene controls the enzyme, which is involved in blood clotting.
A patient comes in with fever, hallucinations, and altered mental status. Labs show Thrombocytopenia Anemia, Proteinuria Diagnosis?
TPP =pentad= C-CNS Neurologic symptoms, R-Renal failure, proteinuria Fever, Thrombocytopenia, plts Anemia hemolytic Microangiopathic, MAHA TPP Thrombotic thrombocytopenic purpura
A patient presents to the emergency department because of acute onset of fever and paresthesia as well as the development of petechiae on his extremities. Physical examination reveals yellowing of the sclerae. Laboratory tests show a hemoglobin level of 9 g/dL and a platelet count of 30,000/mm³. A peripheral blood smear is shown in the image. Laboratory tests show a hemoglobin level of Hb 9 g/dL Plts count 30,000/mm³. peripheral blood smear Is shown in the image. What is the function of the Protein deficient in this patient?
TPP is =Pentad= 1) Neurologic symptoms, 2) Fever 3) Renal failure, proteinuria 4) Thrombocytopenia, plts count 5) Microangiopathic hemolytic anemia (MAHA), sclerae Jaundice HEMOLYSIS sings by yellowing of the sclerae Jaundice, also known as icterus METALLOPROTEASE —is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor vWf —also known as VON WILLEBRAND FACTOR-CLEAVING PROTEASE (VWFCP —A lack of activity in the ADAMTS13 enzyme protein in the blood causes thrombotic thrombocytopenic purpura (TTP). Metalloprotease a.k.a A Disintegrin And Metalloproteinase The ADAMTS13 gene controls the enzyme, which is involved in blood clotting.
A patient comes in with fever, hallucinations, and Altered mental status. Labs show Anemia, Proteinuria, Thrombocytopenia. Diagnosis?
TTP Thrombotic thrombocytopenic purpura =Pentad= 1) Neurologic symptoms, 2) Fever 3) Renal failure, 4) Thrombocytopenia, 5) Microangiopathic hemolytic anemia (MAHA)
What is the role that von Willebrand factor multimers play in the development of thrombotic thrombocytopenic purpura?
The large vWF multimers cause increased platelet adhesion leading to increased platelet aggregation and thrombosis
Platelets form a clot
The largest multimers are found in the in endothelial cell Weibel-Palade bodies and Platelet α-granules which serve to store VWF prior to its export in the circulation
What are some of the reasons platelets do not work as they should
There may not be enough platelets Normal amount of Platelets but they might not be functioning Platelets may not be able to stick to the blood vessel or to each other Platelets are sometimes not able to send or receive the chemical signals
A woman with schistocytes on Blood Smear and High LDH and bleeding time Is found to have inhibitory antibodies against ADAMTS 13. Treatment?
This is TPP Thrombotic thrombocytopenic purpura Plasmapheresis, steroids
A thrombocytopenic woman's bone marrow biopsy Shows large and numerous megakaryocytes. If you want to treat her, what are your options?
This is immune thrombocytopenia Steroids, intravenous immunoglobulin
Where is vWF present
vWF is present in the subendothelial matrix of normal blood vessels. vWF also circulate as a complex. Factor VIII takes part in the coagulation cascade by activating factor VON WILLEBRAND FACTOR-CLEAVING PROTEASE (VWFCP) or ADAMTS13 enzyme —is a zinc-containing METALLOPROTEASE ENZYME That cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. —The lack of activity in the ADAMTS13 enzyme-protein that circulates in the blood CAUSES TTP
