Worksheet Questions 1/3

Primary Hemostasis Mechanisms

• The three mechanisms of primary hemostasis are activation, adhesion, and aggregation.

Platelet Adhesion

• Platelet adhesion needs the endothelial cell layer to be exposed.
• Von Willebrand factor (VWF) is needed as an attachment factor to collagen receptors.

Mediators for Platelet Aggregation

• ADP and Tromboxane A2 are synthesized and released during platelet activation.
• These mediators recruit additional platelets for aggregation.

Platelet Aggregation

• Fibrinogen is responsible for linking platelets together during aggregation.

Secondary Hemostasis

• Secondary hemostasis is the formation of a cross-linked and water-insoluble fibrin clot.

Vitamin K Dependent Clotting Factors

• The Vitamin K dependent clotting factors are 2, 7, 9, and 10.

Extrinsic Coagulation Pathway

• Factor 3, also known as tissue factor, is the primary initiator of coagulation in the extrinsic pathway.

Extrinsic Coagulation Pathway Equation

• 3 + 7 = 10

Intrinsic Coagulation Pathway Equation

• 12, 11, 9, 8 = 10

Final Common Pathway

• The final common pathway leading to clot stabilization is 5 * 2 * 1 = 13.

Prothrombin Time (PT)

• PT measures coagulation along the extrinsic pathway.
• The normal PT value is 11-14.

Activated Partial Thromboplastin Time (aPTT)

• Activated partial thromboplastin time (aPTT) measures coagulation along the intrinsic pathway.
• The normal aPTT value is 25-35.

Activated Clotting Time (ACT)

• Activated clotting time (ACT) measures the activity of Heparin and Fonda.
• ACT involves the intrinsic and common pathways.

Unfractionated Heparin Mechanism of Action

• The mechanism of action of unfractionated heparin is to strengthen Antithrombin III (AT3).

Holding Unfractionated Heparin

• Unfractionated heparin should be held for 4-24 hours prior to neuraxial anesthesia for a therapeutic dose

Heparin-Induced Thrombocytopenia (HIT)

• HIT pathophysiology involves an antibody against factor 4.

Low-Molecular-Weight Heparin Risks

• Use of low-molecular-weight heparin places the patient at risk for spinal and epidural hematoma.

Warfarin Mechanism of Action

• Warfarin inhibits Vitamin K by Vitamin K epoxide reductase.
• Warfarin inhibits factors 2, 7, 9, and 10.

Warfarin INR Target Value

• The target INR value for warfarin therapy is 2-4.

Warfarin Discontinuation Before Surgery

• Warfarin should be held for 4 days before surgery.

Bivalirudin and Argatroban

• Bivalirudin and argatroban bind and inhibit factor 2.

Xarelto and Apixaban

• Xarelto and Apixaban bind and inhibit factor Xa.
• When given to patients with atrial fibrillation, they reduce the risk of stroke.

Aspirin's Mechanism of Action

• Aspirin blocks Cox 1 and 2, inhibiting Thromboxane A2.

Clopidogrel Discontinuation

• Clopidogrel should be discontinued 5-7 days prior to surgery and regional anesthesia.

Thrombolytics Contraindication

• Plasminogen activator thrombolytics are contraindicated within 24 hours surrounding neuraxial and regional anesthesia.

Antithrombin III Functions

• Antithrombin III binds to and deactivates platelet factors.

Antithrombin III Cofactor

• Antithrombin III is a cofactor for Heparin.

Plasminogen Activators

• Plasminogen activators (tPA, uPA) increase plasmin formation.
• Plasmin results in the breakdown of fibrin clots.

Epsilon Aminocaproic Acid (Amicar)

• Epsilon aminocaproic acid (Amicar) binds to and inhibits plasmin.

Tranexamic Acid (TXA)

• Tranexamic acid (TXA) inhibits plasmin.

Protamine

• Protamine reverses unfractionated Heparin.
• Protamine is a basic drug.
• Protamine is not effective against low molecular heparin.

Risks of Protamine

• Hypertension, anaphylaxis, patient uses NPH insulin, right side HF and acute pulmonary vasoconstriction are major side effects.

Desmopressin Dosage and Effects

• Desmopressin is given in a dose of 0.3 over 15-30 minutes.
• Desmopressin releases endogenous stores of factor 8 or vWF.

Cryoprecipitate

• Cryoprecipitate is given to treat low fibrinogen levels.
• 1 unit/10 kg of Cryoprecipitate increases fibrinogen levels by approximately 50-70 d/l.

Major Intracellular Ions

• Potassium is the major cation and phosphate is the major anion in the intracellular fluid compartment.

Major Extracellular Ions

• Sodium is the major cation and chloride is the major anion in the extracellular fluid compartment.

Barriers in Fluid Compartments

• Cell membranes and the glycocalyx layer prevent free movement of proteins and large macromolecules between body fluid compartments.

"Static Parameters" for Intravascular Volume

• Urine output, heart rate (HR), and respiratory rate (RR) are "static parameters" for monitoring intravascular volume status.

Fluid Replacement Indication

• Greater than 10-12% variation in dynamic parameters like pulse pressure variation with respiration indicates the need for fluid replacement.

Balanced Crystalloid

• Lactated Ringers (LR) is a balanced crystalloid.

Strong Ion Difference (SID)

• SID is the difference between positive and negative ions.
• High SID (↑ Na⁺, Ca²⁺, K⁺, Phos⁻) leads to alkalosis
• Low SID (↑ Cl⁻, Lactate from LR) leads to acidosis.

Effect of Decreased SID on pH

• A decrease in SID leads to acidosis.

Decrease in SID

• A decrease in SID may occur following excessive infusion of normal saline.

Infused Crystalloid Retention

• Approximately 20% of infused crystalloids remain intravascular in healthy patients.

Hypotonic Crystalloids

• ½ NS and D5 in Water are examples of hypotonic crystalloids.
• Water moves into the cell with hypotonic crystalloids.

Hypertonic Crystalloids

• 3% NS and D5W in NS are examples of hypertonic crystalloids.
• Water moves out of the cell with hypertonic crystalloids.

Colloids Defined

• Fluid solutions containing large molecular weight particles suspended in a crystalloid solution are known as colloids.

Albumin Infusions

• Anaphylactoid reactions to albumin infusions are not common.

Populations Sensitive to Hydroxyethyl Starches (HES)

• Renal failure patients, heart failure patients, critically ill patients, open-heart patients and coagulopathy patients should not receive HES

Colloid Superiority

• Evidence does not suggest that colloids are superior to balanced crystalloids for maintaining intravascular fluid volume status.

Functions of Sodium

• Sodium plays a role in membrane potential for excitability and tissue excitability.

Essential Electrolyte

• Potassium is important in cell membrane excitability, vasodilation, clot formation, and renal function.

Drugs Decreasing Potassium Levels

• Insulin, sodium bicarbonate, Kayexalate, dialysis, furosemide, calcium, and beta agonists can decrease potassium levels.

Magnesium

• Magnesium may be used to treat preeclampsia.

Calcium Chloride vs. Calcium Gluconate

• Calcium chloride contains 3x more elemental calcium per ml than calcium gluconate.

Risk of Calcium Chloride

• The risk of giving calcium chloride in small, peripheral IVs is extravasation.

Blood Cell Production

• The kidney/bone marrow is the main source of blood cell production.

Agglutinogen

• An agglutinogen is an antigen that can form agglutinin when exposed to an antibody.

Agglutinin

• Agglutinin is the formation of agglutination.

Agglutination Risks

• The ultimate risks of agglutination are blood clots and adverse effects of blood incompatibility.

Depleted Substances in Stored RBCs

• ATP and 2,3-DPG are depleted as RBCs age in blood storage.

Fluids to Avoid During Transfusion

• D5 and LR should be avoided as carrier fluids for RBC transfusion.

Thawed Plasma Transfusion

• Thawed plasma should be transfused within 24 hours.

Cryoprecipitate Composition

• Cryoprecipitate is rich in factors 1, 8, and 13.
• Cryoprecipitate should not be administered with Platelate

Leukoreduction

• Leukoreduction minimizes leucocytes.
• Leukoreduction reduces WBCs to avoid inflammatory response or donor tissue rejection.

Transfusion-Associated Circulatory Overload (TACO)

• Cardiogenic volume overload related to blood product transfusion is known as TACO.

Transfusion-Related Acute Lung Injury (TRALI)

• Pulmonary vascular injury and non-cardiogenic edema within 6 hours of transfusion is known as TRALI.

Coagulopathy Worsening Conditions

• Coagulopathies from massive trauma are worsened by dilation coagulopathy and fibrinolysis.

TEG

• Thromboelastography (TEG) provides information on clot strength and formation, promoting goal-directed management of coagulopathies.

Electrolyte Replacement

• Calcium should be replaced and monitored with massive transfusion.

Massive Transfusion Defined

• Massive transfusion involves administering greater than 10 units of RBCs in 24 hours.

Balanced Transfusion Ratio

• The 1:1:1 transfusion ratio is 1 PRBC, 1 Plasma, 1 Platelet.

Risks of Excessive Crystalloid Use

• Volume dilution and electrolyte imbalance are risks of excessive crystalloid use for volume expansion during massive hemorrhage/trauma.

Across Answers

• Lactated Ringers and Plasmalyte are examples of isotonic crystalloids.
• Hypocalcemia during massive blood transfusion is related to citrate toxicity.
• Acute onset dyspnea associated with cardiogenic volume exacerbation is characteristic of what transfusion disorder (TACO).
• Magnesium may be given to the patient with preeclampsia for vasodilation.
• These crystalloids hyperosmolar, increasing the osmolality of the extracellular fluid.
• The primary source of blood products is the kidney/bone marrow.
• Coagulopathy is associated with traumatic hemorrhage and excessive volume resuscitation with fluids.
• Macrophages destroy aged RBCs.
• Lipids can be implicated as a trigger for inflammation in TRALI.
• Gluconate provides 27 mg/ml of elemental calcium.
• Calcium can be given in hyperkalemia to reverse cardiac conduction and contractility effects.
• HES colloids have been associated with renal dysfunction earning them a black box warning.

Down Answers

• Cryoprecipitate should not be transfused with platelets
• Albumin colloid is produced from human blood and pasteurized to reduce viral infection.
• Antigen-antibody blood transfusion reactions cause agglutinogens particle aggregation when mixed.
• Platelets are leucoreduced or gamma-irradiated decrease the risk of graft-versus-host disease
• Alkalosis pH imbalance decreases renal K+ secretion
• Sodium is the major extracellular fluid compartment cation
• Lactic acid is a dynamic parameter that may indicate reduced global tissue perfusion
• Use of dextrose-containing or hypotonic solutions leads to RBC lysis

Across Hematologic Pharmacology II Crossword Answers

• Warfarin antagonizes Vitamin K.
• Protamine procoagulant drug works by acid-base neutralization.
• aPTT or ACT monitors heparinization
• Streptokinase and urokinase are plasminogen activators.
• INR is one of the lab tests for monitoring warfarin therapy.
• Plasmin breaks down the fibrin clot to maintain vascular patency.
• Trauma to the blood itself activates the intrinsic coagulation pathway.
• Tranexamic acid (TxA) competes to inhibits the conversion of plasminogen to plasmin reduces the need for RBC transfusion intraoperatively
• Heparin target aPTT is 1.5 - 2.5x normal

Down Hematologic Pharmacology II Crossword Answers

• Calcium is coagulation Factor IV.
• Activation is the first step in formation of the platelet plug.
• DDAVP releases endogenous stores of von Willebrand Factor
• Antithrombin V binds to and inhibits Factors Ila and Xa
• Thrombelastography (TEG) measures clot formation, strength, and lysis
• Factor 2 directly inhibits activated blotting
• Fibrinogen is the first clotting factor to link platelets during aggregation
• Extrinsic is the coagulation pathway that factors III and VII are part of
• Clopidogrel is the antiplatelet drugs
• Aspirin effects persist for the platelet lifespan (7-10 days)

Renal - Diuretics 1 - Mannitol

• A 71-year-old patient, Mrs. S, with a history of cerebral edema, hypertension, and GERD, requires a preoperative diuretic for cerebral edema management.
• Mannitol given.
• Mannitol's mechanism involves increasing plasma osmolality, pulling H2O, and scavenging free O2 radicals.
• The patient's total body water is 42L, and mannitol increases the extracellular fluid compartment.
• Mannitol primarily works in the proximal convoluted tubule (PCT) and descending limb (DL) of the kidney.
• Mannitol is administered at 1/g kg/ 10-15 min with an effect 60-90 min later before incision.
• A 0.2-2g/kg range is a possible dosage as well
• Mannitol may increase blood pressure (BP) by increasing plasma volume.

Renal - Diuretics 2 - Furosemide

• A 41-year-old patient, Miss Y, undergoing robotic hysterectomy requires a diuretic to produce urine before discharge.
• The goal is to avoid hypovolemia and hypotension.
• Furosemide 10-20 mg is a loop diuretic of choice.
• Cefazolin may increase the risk of adverse effects, being nephrotoxic and autotoxic.
• Propofol, rocuronium, and fentanyl have no diuretic effects
• Assess for ototoxocity and tinnitus receptor side effects of the furosemide
• Potential causes of failing to produce urine include hypovolemia, hypotension, hypokalemia and nephrotoxic effects.
• Medication options: Acetylcysteine (Mucomyst) if nephrotoxicity is suspected.
• Addition of thiazide for RAAS activation.
• Also fluids - LR - NS
• Possible RAAS – resistance
• Repeat dose 20-40 mg.

F & E – Fluid Management - Ms. E and Fluid Responsiveness

• 60-year-old Ms. E is undergoing open femur reduction with a history of uncontrolled HTN and chronic renal insufficiency (no dialysis).
• Estimated blood loss is 100ml with two PIVs in place
• Current vitals indicate sinus rhythm but hypotensive but O2sat of 97% from being on a vent.
• The extracellular compartment is 80% interstitial fluid and 20% plasma.
• Pulse Pressure Variation (PP variation) is used to monitor BP trends.
• The dynamic parameters vary around 15%, suggesting fluid responsiveness. 200-500 LR is given to improve parameters.
• Ms. E's BP rebounded after volume administration, but sinus tachycardia and continued hypotension persist with blood loss of 800ml. Further actions should address further fluid responsiveness.
• PRBC/colloid transfusion is considered.
• Administer 2 units of PRBC if H/H has declined
• Albumin administration is also appropriate.
• LR lacks Calcium and NS lacks Potassium.
• A major risk of administering old red cells is potassium leak.
• Following interventions, ionized calcium is checked.
• Hypocalcemia is significant due to large blood loss during femur surgery. Calcium gluconate may be warranted.

F & E – Transfusion Management - Mr. L, Trauma

• 20-year-old Mr. L, a trauma patient with active abdominal bleeding after a motor vehicle crash, has received 2 liters of normal saline and 2 units of PRBCs.
• The patient is sinus tachycardic, hypotensive, with a low temperature and acidemia.
• After attempting hemostasis and transfusing 2 PRBCs, H/H is 6/18, Plt is 45,000, and FGN is 65.
• The team is waiting on TEG and coagulation results.
• Consider PRBC, Cyro, Platelet
• Massive transfusion is considered after 10 units in 24 hours
• NS, Plasmalyte or Norm sol are best during hemorrhage and transfusion
• After resuscitation with NS, Mr. L may be suffering from dilutional coagulopathy.
• Administer FFP and prioritize blood products
• NS contains 154 mEq/L of sodium and chloride.
• LR contains 4 mEq/L of potassium.
• Non-blood product drugs to consider include 1 gram TXA and 1 gram Calcium,

Miss O

• Miss O is at 4pm, is a patient in labor, with regular contractions with a history of vape and DVTs, is medicated prenatals and prohpyalctic low moleulcar wt. HEparin the last being at 8am.
• Epidual cannot be performed until 6pm, preferably 10-12 hrs
• Risk is epidural hematoma and no protamine reversal
• The platelet counts are 125,000, down from 200,000, which cannot be confirmed for HIT since there are no bodies identified
• APTT is at 45 seconds no action is required but monitoring Xa is recommended
• LMWH dose was at 8am
• And needs to describe the intrinsic pathway

Mrs. U

• Mrs. U, patient presented to AV fisture revision surgery.
• U has a past medical history of chronic renal failure with hemodialysis, atrial fibrillation, transient ischemic attack and uncontrolled hypertesnion
• Current meds: torsemide, warafin and amlodipine
• Friday morning latest warfarin hold unless Wednesday preferred
• Bioavailabilty is 100%
• Medication indication: AML - CCB; Warfarin - VTE and Torsemide for fluid retention
• Warfarin: Factors Ex and Common
• INr is at 2.0: so continue process.

RENAL PHARMA CROSSWORD Across

• Acetazolamide primarily works in the PCT
• The osmolality of iodinated contrast Media is related to chemical structure. The lower it is, the lower the risk if adverese events
• In high concentrations, methylene blue is formed by MetHb
• Iodinated contrast media can have a negative inotropic effect on the myocardium
• Hypokalemia may be caused by Ileus
• Triamterene is an example of a diurectic, ENAC abbrev.
• Spironolactone receptor antagonist Aldosterone
• Loop direceicts block Na/K/2ci co transporter
• Manntitol Osmotic diertec decreasing elevated intracranial pressures
• Acetazolamide, carbonic anhydrase, Metabolic Acidosis
• ANP hormone related respond to increase elimination from Na
• Renin Juxtaglomerular hormone to reduced renal perforusion

RENAL PHARMA CROSSWORD Down

• Hypokalemia common electrolyte imbalance
• Loop diuretics are mediators that do Prostaglandins
• ICG IV dye
• Diphenhyrdromaine-1 (H1) blocker agents to reduce reactions
• Biacarbonate Main kidney reaborse
• Contrast Induced Nephropiathy due to vasoconstriction
• Fenoldopam a fast action selective domapin
• Hydrochlorothiazide may cause Allkolosis
• Inert osmostics properties with osmostics
• Calcium increase from Thiazides

Renal Diruretics

• Kidneys create Calciterol, renin and Erythropoietin.
• 25% kidney cardiac output
• Aldosterone causes Na+, water absorption distally, excretion of K+
• HYPERtension and hypervolemia activate the renin-aniotonsin-aldosterone system
• Hypotension and hyponatremia activate the system
• Renin caused by juxtamedullary cell
• Angiotensin II lead to vasoconstriction
• NaCl, h2o resorbed
• Hyperkalemia, Hypovolemia causes arginine, vasopressin and aldosterone.
• Natriuretic, vasodilation and diureis atrial natriuretic properties
• Bicarb reabsorbtion is kidneys
• Filtraition small diuresis
• Afferent are arterioles dilating
• Water follows sodium
• ATP NA+, K+
• osmosis passive
• loop direretics inhibit NACL ascending thick loimb