Term
| 3 components of normal hemostatic system: |
|
Definition
- vessel wall
- circulating blood platelets
- blood coagulation and fibrinolysis |
|
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Term
| Platelets are disk shaped cells that arise from ___ in bone marrow. 1/3 of platelets are sequestered in the __, the other 2/3 circulate for 7-10 days. Platelets are responsible for __ hemostasis. Normal platelet count is : |
|
Definition
- megakaryocytes
- spleen
- primary hemostasis
- 150,000- 400,000 |
|
|
Term
| hematopoietic stem cell> megakaryoblast> megakaryocyte> (fragmentation of cytoplasm)> platelets |
|
Definition
|
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Term
| ___ is the regulator of platelet production and is produced by the liver and kidneys. It increases the __ and __ of maturation of mekaryocytes. Levels are increased with __ and decreased with ___. |
|
Definition
- Thrombopoietin
- number and rate of matauration
- increaed with thrombocytopenia
- decreased with thrombocytosis |
|
|
Term
| 250,00 platelets is normal. half life of 8-10 days |
|
Definition
|
|
Term
| Platelets have a __ coat made of __. This is important for interaction of platelets or other aggregating agents. They are full of __ __ and a __ __. |
|
Definition
- mucopolysaccharide coat
- glycoprotein
- alpha granules
- dense core |
|
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Term
| Platelets are responsible for forming the mechanical plug during the hemostatic response to vascular injury. The main steps are __, __, and __. |
|
Definition
- adhesion
- release
- aggregation |
|
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Term
| Adhesion of platelets to the subendothelial __ is dependent on __ _ _and __. |
|
Definition
- collagen
- von Willebrand factor
- glycoproteins |
|
|
Term
| Platelet release/excretion occurs when __ exposure results in release of __ contents which include __, __, and __. The __ and __ activate __ synthesis. |
|
Definition
- collagen exposure
- ADP, serotonin, and fibrinogen
- collagen and thrombin activate prostaglandin synthesis. |
|
|
Term
| Release of __ and __ leads to AGGREGATION which is followed by more secretion leading to secondary aggregation leading to a platelet mass or plug. |
|
Definition
- Thromboxane A2 and ADP
(TXA2 potentiates aggregation and is a vasoconstrictor) |
|
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Term
| __ disorders are the most common cause of bleeding. The d/o could be due to decreased number (thrombocytopenia) or defective function. |
|
Definition
|
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Term
| Thrombocytopenia decreased production causes: |
|
Definition
- Marrow Damage: drugs, aplasia, malignancy
- Congenital defects
- Ineffective production: B12 or folic acid deficiency |
|
|
Term
| Thrombocytopenia increased destruction causes: |
|
Definition
- Non-immune: DIC, TTP, HELLP
- Immune: ITP, HIT, SLE, AIDs, TTP |
|
|
Term
Autoimmune disorder characterized by
platelet bound antibodies:
Classification:
Acute: Usually in children, self limiting preceeded by infection usually viral.
Chronic: Usually in adults, more common in female. |
|
Definition
| Immunothrombocytopenia (ITP) |
|
|
Term
| pathogenesis of immunothrombocytopenia: |
|
Definition
Platelets are sensitized with autoantibodies.
Premature removal of platelets from the circulation by macrophages of the R-E system and destroyed mainly in the spleen. |
|
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Term
| Immunothrombocytopenia (ITP) manifestations: |
|
Definition
Skin purpura, superfacial bruising, epistaxis, menorrhagia.
Mucossal hemorrhage is seen in severe cases and intra-cranial hemorrhage is rare.
Splenomegaly: 10% of cases. |
|
|
Term
|
Definition
primary immune thrombocytopenic purpura
autoimmune thrombocytopenic purpura |
|
|
Term
| Isolated thrombocytopenia with normal bone marrow and the absence of other causes of thrombocytopenia: |
|
Definition
|
|
Term
|
Definition
Self limiting usually weeks.
In children.
Usually preceeded by viral infection.
Bone marrow shows normal or increased megakaryocytes.
Abrupt onset
Due to immune complexes bound to platelets. (Complex = viral antigen-antibody complex). These complexes are removed by the reticuloendothelial system (RE system).
5-10% can go into chronic ITP. |
|
|
Term
|
Definition
Pathogenesis:
Autoimmune. Antibodies are formed
against antigens on platelet surface.
Clinical:
Usually adults, young female 15-50 yrs.
Insidious onset.
Chronic: last months or years.
No precipitating causes.
Shows fluctuating (cyclical) course with periods in which platelets number return to normal. |
|
|
Term
| Features consistent with ITP dx: |
|
Definition
Thrombocytopenia with normal or slightly large platelets
Normal RBC morphology and number (may have associated iron def or thallasemia etc.)
Normal white cell number and morphology
Splenomegaly rare |
|
|
Term
| laboratory evaluation of ITP: |
|
Definition
May not be helpful
Platelet associated immunoglobulin reflect plasma concentration and alpha granule concentration
Bone Marrow not very helpful as initial test
TSH and HIV test helpful
Peripheral Smear helpful |
|
|
Term
Most patients with ITP do not have clinically significant bleeding
In asymptomatic patients with platelets counts greater then 20 K observation is reasonable |
|
Definition
|
|
Term
| Acute pharmacological tmt of ITP: |
|
Definition
- STEROIDS: prednison 1mg/kg/daily with taper over 2-3 months, Decadron 40mg/d x 4 days, Solumedrol 1gm/day x 2 days
- ANTIBODIES: IVIG, Anti-D |
|
|
Term
| Thrombotic Thrombocytopenia Purpura is a a disorder of __ ___ that affects 4 million per year, usually young adults and females. Untreated mortality rate is greater than ___. |
|
Definition
- von Willebrand Factor proteolysis
- 90% |
|
|
Term
| TTP is aka ___ __ __ in which __ RBCs with __ __ and one or several __ RBCs in high power oil, greater than 1% total RBCs. The thrombocytopenia presents with ___,__ abnormalities like elevated __ and __, __ changes, ___, and __ which results in __ and increased LDH. |
|
Definition
- microangiopathic hemolytic anemia
- fragmented RBCs with intravascular clumping
- fragmented
- petechiae
- renal abnormalities like elevated BUN and Cr
- neurological changes
- fever
- hemolysis which results in anemia in increased LDH |
|
|
Term
|
Definition
- plasma exchange with fresh frozen plasma
- response is 70-90% |
|
|
Term
| Lab manifestations of TTP: |
|
Definition
- thrombocytopenia range of 100,ooo to 300,000
- elevated LDH
- initially coagulation studies are normal |
|
|
Term
|
Definition
Infusion of FFP 30 cc/kg/day until ready for plasma exchange
Daily plasma exchange with either FFP or cryopoor FFP (45 to 55 cc/kg/day)
Steroids (Prednisone 1 mg/kg/day)
Red Blood Cells if needed
Platelets only if absolutely necessary |
|
|
Term
| HIT is the presence of a __ complex between __ __ _ and __. HIT is associated with __ despite profound ___. |
|
Definition
- multimolecular complex between platelet factor 4 and heparin
- thrombosis despite profound thrombocytopenia |
|
|
Term
| HIT pts have/do not have petechiae. |
|
Definition
|
|
Term
| HIT onset is between __ and __ days after exposure to heparin, sooner if been previously exposed. Thrombocytopenia between __ and __. Greater than 50% develop thrombosis, both __ and __. |
|
Definition
- 5 and 10
- 15,000 and 150,000
- venous and arterial |
|
|
Term
| One should clinically supsect HIT if see a greater than __ drop in platelets in the setting of heparin use. Even in absesne of thrombosis, these patients should still get __ __ __. |
|
Definition
- 50%
- lower extremity dopplers |
|
|
Term
|
Definition
- removal of all heparin products
- begin Direct Thrombin Inhibitor (argatroban or refludan)
- treat with DTI until platelet count normalizes, then begin anticoagulation with coumadin |
|
|
Term
| __ __ __ and __ aka DIC, is a coagulation disorder caused by widespread activation of the __ __ . Generation of __ __ occurs. __ and __ get consumed. Unregulated hemostasis and thrombosis occurs. Organ ischemia and infarction occurs. This life threatening. Tmt depends on etiology. |
|
Definition
- Disseminated Intravascular Coagulation and Fibrinolyis
- clotting mechanism
- intravascular fibrin
- Procoagulants and platelets |
|
|
Term
| Henoch-Schonlein Purpura is more common in __ than __ and is often between the ages __ and __. An __ precedes dx in 2/3 of children. Vasculitis of HSP involves the small vessels of the __, __ _, and __. This involves __ immune complexes being deposited in the tissues of these organs. |
|
Definition
- males than females
- 2 and 7 years
- URI
- skin, GI tract, and kidneys
- IgA mediated immune complexes |
|
|
Term
Dx based off of this:
- classic palpable purpuric rash
- polyarthralgia/polyarthritis in ankles and knees
- sharp abdominal pain
- hemorrhage/intussuseption
- renal problems
- hypertension
- testicular torsion: |
|
Definition
|
|
Term
UA may show blood and proteinuria
Stool may be positive for occult blood
Antistreptolysin O (ASO) titer may be elevated
+/- GABHS in throat culture
Serum IgA may be elevated |
|
Definition
|
|
Term
|
Definition
- supportive
- daily clinical visits until HSP clears
- UA PRN
- Motrin po 2.5 tsp every 6 hours for pain/fever
- elevate legs
- corticosteroids may be helpful for GI/joint symptoms, use is cautioned |
|
|
Term
| 4 classifications of anti-platelet drugs: |
|
Definition
- Aspirin
- P2Y12 Antagonists
- Dipyridamole
- GPIIb/IIIa Antagonists |
|
|
Term
| ASA is the most widely used antiplatelet drug. It acts by inhibiting the synthesis of ___. |
|
Definition
|
|
Term
| P2Y12 Antagonists aka __ __ Antagonists are beneficial in the tmt and prevention of __ and the prevention of __ events. These drugs include __ and ___. |
|
Definition
- ADP receptor antagonists
- ACS
- thrombolic
- Clopidogrel and Ticlopidine
(Prasugrel and Cangrelor and AZD6140 are in phase III clinical development |
|
|
Term
| Dipyridamole increases the levels of second messengers __ and __ within platelets. This is used as __ prevention in patients following __, often in combination with __ |
|
Definition
- cAMP and cGMP
- secondary prevention in patients following stroke
- combinatin with Aspirin |
|
|
Term
| Glycoprotein IIb and IIIa antagonists inhibit the binding of __ to its __, thereby inhibiting __ __ but not __ __. These are given __ and are effective during _ __ __. |
|
Definition
- fibrinogen to its receptor
- inhibiting platelet aggregation but NOT platelet activation
- IV
- Percutaneous Coronary Intervention (PCI) |
|
|
Term
Thromboxane A2 is synthesized in platelets, from which it can be released. Thromboxane A2 causes vasoconstriction and is also a platelet agonist.
ASA BLOCKS THROMBOXANE GENERATION. SEE PREVIOUS SLIDE FOR FURTHER EXPLANATION.
ASA ACTIONS ARE IRREVERIBLE.
IBUPROFEN AND NEPROXEN ALSO AFFECT THROMBOXANE, BUT THEIR EFFECTS ARE REVERSIBLE.
PATIENT NEEDS TO BE OFF ASA A WEEK TO 10 DAYS BEFORE SURGERY. THE NAPROXEN AND IBUPROFEN JUST NEED TO BE OFF OF THEM 2-3 DAYS BEFORE SURGERY. |
|
Definition
|
|
Term
| When TXA2 binds to its receptor, the platelets are __. Aspirin __ binds ___, an enzyme in platelets that makes thrombonxane a2. Thus as ASA downregulates the synthesis of TXA2 it will also inhibit __ __. |
|
Definition
- activated
- irreversibly cylco-oxygenase
- platelet activation |
|
|
Term
Rapid absorption of aspirin occurs in the stomach and upper intestine, with the peak plasma concentration being achieved 15-20 minutes after administration (What property of ASA promotes this?)
The peak inhibitory effect on platelet aggregation is apparent approximately one hour post-administration
Aspirin produces the irreversible inhibition of the enzyme cyclo-oxygenase and therefore causes irreversible inhibition of platelets for the rest of their lifespan (7 days) |
|
Definition
| ASA can be absorbed in the stomach b/c it it is a weak acid |
|
|
Term
|
Definition
- Prevention of ischemic events in patients with angina pectoris
- Prevention of coronary artery bypass graft (CABG) occlusion
- Secondary prevention of transient ischemic attacks (TIAs), ischemic stroke, and myocardial infarction |
|
|
Term
|
Definition
- risk of GI adverse events (ulceration and bleeding)
- allergic reactions
- not a very effective antithrombotic drug, but widely used b/c of ease of use
- aspirin resistance in some patients (lack of response)
- irreversible platelet inhibition |
|
|
Term
| __ and __ are ADP receptor antagonists that ___ inhibit the ADP receptor. |
|
Definition
- Ticlopidine and Clopidogrel
- irreversibly |
|
|
Term
| ADP antagonists prevent __ __ induced by ADP. |
|
Definition
|
|
Term
|
Definition
- secondary prevention of ischemic complications after MI, ischemic stroke, and established peripheral artery disease
- Secondary prevention of ischemic complications in patients with acute coronary syndrome (ACS) without ST elevation |
|
|
Term
| ADP receptor major drawbacks: |
|
Definition
- Clopidogrel only slightly more effective than aspirin
- Some pts have resistance to Clopidogrel tmt |
|
|
Term
| Dipyridamole increases the levels of __ available for binding platelets by inhibiting __ uptake in RBCs and endothelial cells. Thus, more ___ will be able to bind __ and thereby prevent activation and aggregation. These drugs increase levels of __ __, __ and __, wihtin platelets. |
|
Definition
- adenosine
- adenosine
- adenosine
- platelets
- second messengers, cAMP and cGMP |
|
|
Term
| Dipyramidole is __ absorbed from the GI tract with peak plasma concentration occuring __ minutes after oral administration. More than __% is bound to plasma proteins. It is metabolized in the __ and mainly excreted as __ in bile and a small amount is excreted in the __. |
|
Definition
- poorly
- 75
- 90
- liver
- glucuronides
- urine |
|
|
Term
|
Definition
| - secondary prevention of ischemic stroke after transient ischemic attack (TIA) or ischemic stroke (usually combo with aspirin) |
|
|
Term
| Drawbacks of Dipyramidole: |
|
Definition
- not very effective antithrombotic drug
- also has vasdilatory effects and should be used with caution in patients with severe coronary artery disease
- chest pain may be aggravated in pts with underlying coronary artery diseae who are receiving dipyridamole |
|
|
Term
The glycoprotein IIb/IIIa receptor is exposed on the platelet membrane after activation and is responsible for mediating platelet aggregation.Once activated, the receptor becomes functional and binds fibrinogen, leading to the formation of platelet aggregates.
Glycoprotein IIb/IIIa receptors therefore mediate the final common pathway of platelet aggregation.GPIIb/IIIa antagonists hava a high affinity for the fibrinogen receptor and prevent binding of fibringoen to its receptor. |
|
Definition
|
|
Term
| GPIIb/IIIa receptor antagonists major use: |
|
Definition
| - prevention of ischemic cardiac complications in patients with acute coronary syndrome (ACS) without ST elevation and during percutaneous coronary interventions (PCI) in combination with ASA and heparin |
|
|
Term
| GPIIb/IIIa receptor antagonist drugs: |
|
Definition
- Abciximab (ReoPro)
- Etifibtide (Integrilin)
- Tirofiban (Aggrastat) |
|
|
Term
| GPIIb/IIIa receptor antagonists drawbacks: |
|
Definition
- can only be administered via IV or infustion and are complicated to manufacture
- |
|
|
Term
| Thrombolytic drugs are used in the acute setting of thromboembolic events to dissolve thrombi. They are administered by intravenous infusion. |
|
Definition
|
|
Term
| Thrombolytic drugs have a common mechanism of converting the ___ __ to the __ __ ___, which lyses the fibrin clot. __ is an active 2 chain polypeptide, is a __ __ ___ capable of breaking down __ as well as __ and __ __ and __. |
|
Definition
- proenzyme plasminogen
- active enzyme plasmin
- Plasmin
- non-specific serine protease
- fibrin
- fibrinogen
- factors V and VIII |
|
|
Term
Thrombolytic drugs catalyse the conversion of the proenzyme plasminogen to plasmin, which, when in proximity to a thrombus or embolus…
Thrombolytic drugs become plasmin and lyse the fibrin
Get these drugs in within 3 hours if suspect a stroke |
|
Definition
|
|
Term
| Thromboembolic drugs degrade fibrin into __ __, known as __ __ __ and _ __, thus dissolving the main body of the clot. These drugs are called clot busters. |
|
Definition
- soluble peptides
- fibrin degradation products (FDP)
- D-dimers |
|
|
Term
| Streptokinase, the first thromboembolic drug, has been replaced by __ __ __ __. __ is naturally occuring but typically manufactured using recombinant DNA technology |
|
Definition
- tissue type plasminogen activator (t-PA)
- t-PA
The third generation thrombolytic drugs, which are recombinant mutant variants of t-PA and have been shown to have comparable efficacy with that of t-PA, have now also reached clinical practice. These include reteplase and tenecteplase. They differ from native t-PA by having increased plasma half-lives that allow more convenient dosing. |
|
|
Term
Thrombolytic drugs:
The plasma half-life of the third generation drugs is 14-45 minutes, allowing administration as a single or double intravenous bolus. This is in contrast to second generation t-PA, which with a half-life of 3-4 minutes, must be administered an initial bolus followed by infusion |
|
Definition
|
|
Term
| Thrombolytic drugs major use: |
|
Definition
Thrombolysis in patients with acute myocardial infarction (MI)
Thrombolysis in patients with ischemic stroke
Thrombolysis of (sub)acute peripheral arterial thrombosis
Thrombolysis in patients with acute massive pulmonary embolism
Thrombolysis of occluded hemodialysis shunts |
|
|
Term
| Thrombolytic drug drawbacks: |
|
Definition
- tmt limited to acute in-hospital tmt
- high risk of bleeding with this tmt
- PATIENT ON ANTICOAGULANTS ARE CI FOR TMT WITH THROMBOLYTICS |
|
|
Term
| Contraindications to Thrombolytic therapy; |
|
Definition
Absolute Contraindications:
- pt on anticoaulants
- recent head trauma
- cranial tumor
- previous hemorrhagic shock
- stroke or CVA events 1 year old
- active internal bleeding
- major surgery within 2 weeks
Relative Contraindications:
- active peptic ulcer
- diabetic retinopathy
- pregnancy
- uncontolled HTN |
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|
