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120 Cards in this Set
- Front
- Back
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What does bleeding time measure?
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platelet response to a LIMITED vascular injury
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What will make bleeding time abnormal?
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deficit in platelet number or function
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What test assesses the function of the extrinisic and common pathways?
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Prothrombbin Time
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What will be elevated with deficiencies in factor VII and /or factors X, V, prothrombin II and fibrinogen I?
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PT
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What test assesses the intrinsic and common pathways?
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Partial Thromboplastin Time (PTT)
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What will cause elevation of PTT?
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deficiciencies in factors VIII, IX, XI, XII and or factors X,V, Pro II, and fib I
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What is a normal platelet count?
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150000 - 450000/mm3
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If platelet count is abnormal, what should be done?
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do PB smear to rule out false thrombocytopenia
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What is a normal PT?
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10-13 sec
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What is a normal PTT?
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25-35 sec
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What are used to clot in plasma for PTT?
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kaolin, cephalin, and Ca
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What can clue to bleeding due to vessel wall abnormalities?
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petechiae and purpura
normal PTT and PT |
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What microbes can cause vasculitis or DIC?
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menigococcus, IE orgs (strep/staph) and rickettsia
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What is a particular term for the kind of hypersensitvity vasculaitis that occurs with drug reactions?
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leukocytoclastic
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What happens in Ehler-Danlos syndrome?
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imparied collagen around the vessel walls causes hemorrhage
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How is cushing syndrome similar to Ehlers-Danlos?
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loss of perivascular support tissue, but this is due to the protein wasting effects of corticosteroids
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What is the name of a vessel wall abnormality that is described by systemic hypersensitvity disease of unknown etiology, which manifests as purpura, colic, polyarhtralgia, and acute glomerulonephritis?
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Henoch-Schonlein purpura
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What is the mechanism of Sx seen in Hencoh-Schonlein purpura?
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immune complex deposition on vessels and glomeruli
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WHat is the name for an autosomal dominant vascular disorder, that causes bleeding in dialted, tortuous, thin walled vessels, and manifests primarily in the mucous mambranes of the nose, mouth, and eyes and GI tract mucosa?
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Hereditary Hemorrhagic Telangiectasia
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What protein is deposited, systemically, from plasma cells in primary amyloidosis?
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AL protein
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Which two tests are ususally normal in the setting of thrombocytopenia?
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PT and PTT
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What can occur at a platelet count of <20,000?
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spontaneous bleeding
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What affect do megalolastic anemias have on platelet production?
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ineffective megakaryocyte production
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How long are platelets viable in transfusable blood?
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24 hours
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What happens in immune thrombocytopenic purpura?
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Chronic ITP
IgG antibodies form against platelet membrane glycoproteins Iib-IIIa or Ib-IX Opsonised platelets are then phagocytosed by mononuclear phagocytes – spleen is the major site of removal There is some evidence to suggest magakarycocyte injury or destruction but this is minor Acute ITP Typically preceeded by a viral illness 2 weeks prior Normal size spleen Congested sinusoids Hyperactivity and enlargement of splenic follicles Bone marrow has increased megakaryocytes |
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What secondary conditions can cause ITP?
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SLE, AIDS, viral infection, drugs
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What is the priamry Ab made against platelets in ITP?
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Chronic ITP
IgG antibodies form against platelet membrane glycoproteins Iib-IIIa or Ib-IX Opsonised platelets are then phagocytosed by mononuclear phagocytes – spleen is the major site of removal There is some evidence to suggest magakarycocyte injury or destruction but this is minor Acute ITP Typically preceeded by a viral illness 2 weeks prior |
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What does IgG do to platelets after binding in ITP?
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opsonizes them
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What is the main treatment for ITP?
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splenectomy
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What test is important in considering differential diagnosis in ITP?
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BM Bx to rule out marrow failure
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What is seen in the spleen in ITP?
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mild snusoidal congestion with megs in sinuses
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What besides primary morpholgy can clue to ITP?
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secondary bleeding in any part of the body
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In what patient population is Idiopathic TP more likely?
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Chronic ITP
Most common in women less than 40 years Female to male 3:1 Acute ITP Childhood disease preceeded by acute viral infection |
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What do platelets in a PB smear of a patient with ITP look like?
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large
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What population of patients does acute ITP occur in?
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abrupt onset after viral illness in childhood
usually 2 wk interval between infection and purpura Abrupt onset Usually self limiting (lasts less than 6 months) 20% go on to develop chronic ITP |
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In acute ITP, what % go on to have chronic ITP?
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~20%
Chronic ITP- Insidious onset Characteristic long history of nose bleeds, easy bruising Bleeding time prolonged PT and APTT normal |
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What drugs are notable for TP risk?
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quinine, quinidine, sulfonamides, and heparin
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How many patients are reciving heparin?
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1/20
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What is the most common drug induced TP?
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type I heparin induced
abrupt moderate severity usually clinically insignificant |
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Which type of drug induced TP is life threatening?
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type II
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What is the mechanism of type II heparing induced TP?
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heparin/platelet factor IV complex reaction
Factor IV binds and activates paltelets whcih leads to thrombosis |
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What is the onset of Type II drug TP?
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delayed onset of 5-14 days
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What is the most common hematologic probem in HIV?
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thrombocytopenia
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What happens in HIV induced TP?
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increased destruction and decreased production
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WHat 2 mechanisms are possible causes of HIV induced TP?
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Megs have CD4 receptors
platelet membrane GP Abs (IIb-IIIa) |
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What adult disease, exhibiting transient neuro deficits and in the setting of some renal failure, has the mechanism of a ADAMTS 13 enzymatic deficieny?
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TTP
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What does ADAMTS 13 normally do when present in adequate amounts?
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degardes HMWK multimers of vWF promoting platelet microaggregation
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What therapy has increased recovery to >80% in TTP?
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plasma exchange therapy
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What close cousin of TTP ususally occurs in children but does not produce neuro deficits and has a course that is dominated by acute renal failure?
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HUS
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What bacterial infection often precedes an episode of HUS?
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E. Coli (o157:H7) producing gastroenteritis
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What can be sometimes irreversible in sever cases of HUS?
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renal damage
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Why does HUS ususally happen in adults?
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secondary to drugs and/or radiation therapy
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What is the usual patholgy of HUS in adults?
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endothelial cell damage that leads to platelet microaggregate formation
prognosisis guarded |
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What two bleeding disorders share the following cahracteristics:
wide spread thrombi of dense platelets in microcirculation decreased platelet count increased bleeding time NORMAL PT and PTT? |
TTP and HUS
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Why do ASA and NSAIDs prolong bleeding time?
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inhibition of cyclooxygenase which suppresses TXA2 and PG synthesis
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Why does uremia cause platelet dysfxn?
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not really known
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What defects occur in congential platelet dysfxn?
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disorders of :
adhesion aggregation secretion |
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What is the name of an AR inherited deficiency of platelet membrane GP complex Ib-IX (vWF receptor), that causes defective adhesion to subendothelial collagen?
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Bernard-Soulier syandrome
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What is the name of the AR deficiency of platelet memebrane GP complex IIb-IIIa?
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Glanzmann thrombasthenia
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What is the normal fxn of GP complex IIb-IIIa?
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create fibrinogen bridges between platelets
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What are "thrombasthenic platelets" unable to do?
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cannot aggregate with ADP, collagen, epinephrine or thrombin
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What is the ususal problem in platlet secretion dysfxn?
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impaired secretion of alpha and dense core granules
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What are normally contained in alpha and dense core granules?
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ADP, TXAs
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What are uncommon in clotting factor abnormalities?
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petechiae and purpura
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What are common clinical features of clotting factor abnormalities?
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ecchymoses or hematomas post trauma
prolonged post op bleeds GI or GU bleeds hemorrhage of weight bearing joints |
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What acquired clotting factor abnormality causes decreased II, VII, IX, and X levelas as well as decreased protein C levels?
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vitamin K deficiency
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What is deficient in Hemophilia A?
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factor VIII
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What factor is deficient in Hemophilia B?
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factor IX
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Where is factor VIII made?
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liver and kidney
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Why is factor VIII necessary?
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factor X activation
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Which is larger VIII or vWF?
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vWF
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Where is vWF made?
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endothelial cells and Megs
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What is the main job of vWF?
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binding to collagen, heparin, and platelet membrane GPs to promote hemostasis
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What carries and stabilizaes factor VIII?
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vWF
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What happens to factor VIII in the absensce or deficiency of vWF?
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t1/2 is decreased by 80%
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How can vWF be measured?
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ristocetin agglutination test
Forms a complex with factor VIII – factor VII required for factor X activation Facilitatesthe adhesion of platelets to endothelium via platelet GpIb-IX |
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Is vWF common?
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yes, very
frequency of ~1% Prolonged bleeding time, normal platelet count Characterised by excessive bleeding from wounds, menorrhagia, spontaneous mucous membrane bleeding |
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How is vWF inherited?
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AD
Several variants Type 1 and 3 have reduced quantities Type 2 has VWF with functional defects VWF produced by endothelial cells Functions Forms a complex with factor VIII – factor VII required for factor X activation Facilitatesthe adhesion of platelets to endothelium via platelet GpIb-IX |
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What is wrong with vWF in VWD?
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low quality or quantity of vWF
One of the most common inherited disorders of bleeding in humans 1% frequency |
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What are the clinical features of vWD?
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spontaneous mucous membrane bleeds
excess bleed from wound or menorrhagia |
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Why is blleding time prolonged in vWD?
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platelats cannot adhere to subendothelial collagen with out vWF
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Why is PTT prolonged in vWD?
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without vWF, factor VIII has avery short t1/2
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Which vWD types exhibit low quantity of vWF?
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types 1 and 3
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Which type of vWD exhibits a qualitative defect in vWF?
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type 2
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Which type of vWD is AD, mild, and represents 70% of most vWD cases?
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type 1
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Which type of vWD is AR, severe and may clinically resemble Hemophila ?
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type 3
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Which subset of type 2 vWD is most common?
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2A
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What is the inheritance pattern of vWD type 2?
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AD, causing missense mutations
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What is missing from the plasma in type 2 vWD?
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large and intermediate multimers that contribute to vWF?
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What is the most common hereditary diease with SERIOUS bleeding?
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Hemophilia A
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What is the inheritance pattern of Hemophilia A?
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X linked recessive: Mostly occurs in males and homozygous females
Can occur in heterozygous females if there is unfavourable lyonisation 30% no family hx |
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Why are there few hetero Hemo A females?
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lyonization of normal X
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What is the pathology of Hemo A?
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reduced quantity or activity of factor VIII
Clinical effect correlates with level of factor VIII <1% severe 2-5% - moderate 6-50% - mild |
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WHat % of patients with Hemo A have no family history (new mutation)?
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30%
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Upon what does the severity of Hemo A depend?
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the activity level of factor VIII
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Upon what does the activity level of factor VIII depend?
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the type of mutation
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When can hemarthrosis occur in type A hemophiliacs?
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everyday wear and tear
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What is the effect of Hemo A on bleeding time, platelet count, and PT?
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none
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What pathway will be affected by Hemo A, how does this show?
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intrinsic path, shows by prolonged PTT
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How is Hemo A diagnosed?
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factor VIII assay
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How is Hemo A treated?
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infusion of recombiant factor VIII
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What can happen in 15% of hemo A patients during a course of traetment?
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Factor VIII Ab development
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What is the inheritance pattern of Hemo B?
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X-linked recessive
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How many Hemo B patients have normal levels or NONFUNCTIONAL factor IX?
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1/7
In 14% factor IX is present but non- functional |
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What is generally the only way to differntiate Hemo A from Hemo B if severe?
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do a factor IX assay
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What is the general concept behind DIC?
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consumption of platelets, fibrin and coagulation factors causes microthrombi, while secondary fibrinollysis causes hemorrhage
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What are the two triggering mechanisms of DIC?
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tissue factor or thromboplastic substance release
widespread endothelial injury |
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What do the following substances have in common?
placenta adenocarcinomic mucus leukemic cell granules gram - endotoxin tissue thromboplastins |
these are all tissue factor/thromboplastic substances
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WHat cytokine causes endothelial cell injury in septic shock?
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TNF
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What event initiates TF release, promotes platelet aggregation and activates the intrinsic pathway?
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endothelial cell injury
Initiating mechanisms Release of tissue factor or thromboplastic substances into the circulation Widespread injury to endothelial cells Consequences: Fibrin deposition in microcirculation Ischaemic injury Microangiopathic haemolytic anaemia Activation of plasmin Haemorrhagic diathesis due to consumption of clotting factors |
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What is the most frequent cause of DIC?
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obstetric complications
50% are obstetric patients 33% have carcinomatosis (DIC tends to develop insidiously) |
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Why does hemolytic anemia result from widespread fibrin deposits in the microcirculation?
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RBC fragmentation in the narrowed microvasculature
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What does FDP do?
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inhibits platelet aggregation and fibrin polymerization
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What is a severe occurrence that can be seen in the kdneys as aresult if DIC?
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bilateral renal cortical necrosis
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What can happen to the adrenal glands in the setting of meningococcemia, secondary to fibrin microthrombi?
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massive adrenal hemorrhage
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What is Sheehan syndrome?
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anterior pituitary necrosis occurring as a result of severe peripartum bleed
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What is the ususal presentation of acute DIC?
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bleeding as a result of obstetric complications or trauma
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What is the usual presentation of chronic DIC?
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thrombotic complications as a result of a carcinomatosis
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What classification of DIC presents with thrombocytopenia
decreased fibrinogen prolonged PT and PTT and Elevated FSP? |
severe acute DIC
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How can acute mild DIC be differntiated from severe on the lab work?
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in acute mild DIC, PT and PTT may be normal
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