Hemostasis Flashcards
Symptoms of Pulmonary Edema
Dyspnea
Orthopnea
Paroxysmal nocturnal dyspnea
Heart Failure Cells
Hemosiderin-laden macrophages in the alveolar spaces that can be seen w/ chronic pulmonary congestion
Process of ecchymosis healing
Hemoglobin (red-blue) =» Bilirubin (blue-green) =» Hemosiderin (gold-brown)
Hemorrage
Can manage up to 20% loss before shock occurs
Sentinal Node Biopsy
Reduces the number of axillary dissections needed for breast-cancer staging =» reduced comorbidity of breast cancer
PFA
Prolonged collagen/EDI; normal collagen/ADP =» Drug induced issue
Prolonged both =» platelet abnormality (possible vWF)
Leukocytoclastic vasculitis
Destruction of the vascular wall due to the deposition of drug-induced immune complexes
Henoch-Schonlein Purpura
Systemic hypersensitivity disease in which immune complexes deposit in the vascular wall
*Colicky abdominal pain, AGN, polyarthralgia
Immune Thrombocytopenic Purpura
Chronic: IgG autoab against platelet that are prominently removed by the spleen (will be congested and have fulminant macros)
*BM will have increased megakaryocytes w/ left-shifted maturation
Treatment: Immunosuppression, rituximab
Acute: Abrupt, normally self-limiting but can progress to acute
Heparin Induced Thrombocytopenia
Type I: Direct platelet aggregation caused by heparin a couple days after administration; common and clinically insignificant
Type II: Abs directed against Platelet Factor 4 complex result in agglutination and thrombosis; **can be life-threatening
-LMW heparin is LESS LIKELY to cause but cannot cure it
TTP
Caused by an ADAMTS deficiency =» accumulation of HMW multimers of vWF and aggregation
Classic pentad: 1. Fever
2. Thrombocytopenia
3. Microangiopathic hemolytic anemia
4. Renal failure
* 5. Neurologic symptoms
Treatment: Plasma exchange to remove antibody
*DO NOT GIVE PLATELETS; MAKES IT WORSE
Hemolytic Uremic Syndrome
Presents as bloody diarrhea and subsequent renal failure following an infection by E.coli 0157:H7
Treatment: Supportive care; plasma exchange
Can suffer irreparable renal damage
Bernard-Soulier Syndrome
Deficiency of platelet Gp-Ib complex where platelets bind to vWF; AR inheritance
*Giant platelets
Labs: Everything can cause aggregation except ristocetin
Glanzmann’s Thrombasthenia
Deficiency of Gp-IIIb-IIa where fibrinogen crosslinks platelets
Labs: Only ristocetin can cause aggregation
vonWillebrand Disease
Most common bleeding disorder that presents as prolonged bleeding from cuts, menorrhagia, and GI bleeding
-Abnormal PFA and PTT
Type I and III =» quantitative (III more severe)
Hemophilia A
Factor VIII deficiency that presents w/ easy bruising, menorrhagia, and *hemarthrosis
Labs: Prolonged PTT
-Will not see mucous membrane bleeding or petechiae
Treatment: Humate P/ recombinant Factor VIII
Christmas Disease
Clinically identical to Hemophilia A but is due to altered/deficient Factor IX
-Prolonged PTT
Treatment: recombinant Factor IX
DIC
Presents as a microangiopathic hemolytic anemia that progresses to SOB, respiratory failure, **RENAL FAILURE, circulatory shock (all related to hypoxia of areas affected)
-Can originate from meningococcemia, APML, Adenocarcinoma, placenta abruption, massive tissue injury
=»Tissue injury and massive Thrombin release cause excessive activation of coag cascade and fibrin deposits in vasculature
Labs: Decreased platelets, fibrinogen
Prolonged PTT and PT
Increased D-dimer
PB: Schistocytes, reticulocytosis, leukocytosis, left shift, thrombocytopenia
*Can cause Waterhouse-Friedrichson Syndrome (meningococcemia) and Sheehan Syndrome along w/ thrombi affecting other areas
Sheehan Sydrome
Postpartum pituitary necrosis; can be caused by DIC
SIRS
“Systemic Inflammatory Response Syndrome”
Exaggerated response of a local inflammatory reaction mediated by TNF-a, IL-1, IL-6 and excessive endothelial cell activation
-Diagnosed by two or more signs of the following: fever, tachcardia, tacypnea, leukocytosis, leukopenia
Trigger for septic shock
Bacterial products that activate TLRs on PMNs
Endothelial Cell Activation during Septic Shock
3 major effects
- Thrombosis (DIC)- Inflammatory mediators stimulate PAI-1 and TF prod.; also decrease TFPI, Protein C, thrombomodulin
- Increased Vascular Permeability- Increases interstitial fluid decreasing the amount of fluid available to the tissues =» hypoxia
- Vasodilation- Increased NA and TXA2
Adult Respiratory Distress Syndrome (Shock)
Can be induced by septic shock when decreased perfusion of the heart =» decreased contractility =» increased pulmonary edema =» lung damage
*Septic shock also damages the kidneys, liver, lungs
Stages of Shock
Nonprogressive- Tissue perfusion is maintained after reflex mechanisms compensate (SIRS)
Progressive- Worsening circulator and metabolic imbalances cause acidosis and organ/tissue damage
Irreversible- Extent of tissue damage is too bad and pt. is done for
Treatment of Septic Shock
Control fluid infection
Vasopressors
Insulin therapy (for induced hyperglycemia and insulin resistance)
Protein C (decrease thrombosis)
Anti-inflammatories
Corticosteroids
Heparin
Reversibly binds to ATIII at an Arg-Ser residue (Coag factors irreversibly bind); must be given IV or subcutaneous injection (IM causes hematoma)
-Also increases LPL activity =» lipid clearance
Indications: Venous thrombosis, pulmonary thromboembolism; **can be given in pregnancy
-Can cause Heparin-Induced Thrombocytopenia
Protamine
Heparin antidote that binds and disables activity
-May be cross-allergic w/ NPH insulin and fish allergies
Enoxaparin (Daltaparin, Tinzaparin)
LMW heparin that is too small to simultaneously bind ATIII and thrombin; is as safe and effective as unfractionated heparin
*Used in pregnant women AND with outpatients
Indications: Prophylaxis and acute thromboembolism
Fondaparinaux
Works the same as enoxaparin (specific inactivation of Factor Xa after binding ATIII; is a pentasaccharide synthetic
Indications: Prophylaxis and acute DVT
*Used in pregnant women
Warfarin
Inhibits the synthesis of BIOLOGICALLY ACTIVE Vitamin-K dependent factors (they are still present tho); does not inhibit clotting in vitro
Indication: Arterial thromboembolism from A-fib prophylactic; post-op on prosthetic heart valves; venous thromboembolism; pulmonary embolism
⭐️DOC ORAL ANTICOAGULANT
Therapeutic INR goal= 2.0-3.0 (+.5 for heart valve replacement)
Drugs that increase effect: Ketoconazole, cephalosporin, Bactrim, cimetidine
…decrease effect: **Rifampin, cholestyramine, penobarbitol, cigarettes
*CYP2C9 mutations, VKORC
Warfarin during pregnancy
1st trimester =» nasal hypoplasia
Later=» CNS issues/death
Argatroban
Directly inhibits the active site of ATIII;
⭐️used in pts. w/ possible HIT
Dagibatran
Pro-form of argibatran (directly inhibits ATIII); pro-drug converted to active form by plasma esterases
-Has less drug interactions as it does not react w/ CYP2C9 but it is a substrate for p-glycoprotein
Indications: Prevention of thrombotic stroke; prevention of stroke due to A-fib
***NO ANTIDOTE =» CAUTION W/ DECREASED RENAL FNXN
Dipyridamole
Inhibits platelet PDE =» Increased cAMP levels
=»inhibition of platelet aggregation
-Commonly used alongside Warfarin
Ticlopidine/Clopidogrel
CLOPY
Binds irreversibly to the ADP P2Y12 receptor (platelets need this and another ADP receptor to activate the GpIIIb-IIa complex)
-form disulfide links on a CYS residue
Indications: Reduced risk of stroke; (clopidogrel) acute coronary syndrome
*Ticoplidine ARs include: agranulocytosis, life-threatening thrombocytopenia
=»Clopidogrel PREFERRED
Cangrelor
Reversibly binds to ADP P2Y12 receptor on platelets; very brief half-life
Abciximab/Eftifibatide
Ab that binds the IIb/IIIa receptor; competitive reversible inhibition used w/ unstable angina or angioplasty procedures
- Abciximab has 24hr half life and much stronger anticoagulant
- Do not use w/ bleeding, Warfarin, thrombocytopenia, surgery
Streptokinase
Forms a complex w/ plasminogen to activate other plasminogen molecules
Indications: Reperfusion of coronary arteries following an MI (use in 4-6hrs)
ARs: Tombolytic state (a2-antiplasmin is overwhelmed), FEVER, bleeding
-Do not use w/ intracranial trauma or diastolic pressure of >110mmHg
Antistreplase
Combination of streptokinase-plasminogen and acylated active site
-Acyl group removed by plasma esterases; induces a less lytic state than streptokinase
Alteplase
rt-PA that activates platelet-bound plasminogen and induces less of a lytic state due to its high specificity
Indications: Reperfusion of coronary arteries following MI, pulmonary thromboembolism
*Tenecteplase= geneticall engineered recombinant w/ even more specificity; more resistant to PAI-1
Aminocaproic acid
Inhibitor of fibrinolysis; competes for lysine binding sites on plasminogen and plasmin =» deactivation
