Hematopoietic System: Part 2

palpation - assessmet

• enlargement of

  • lymph nodes

  • spleen

  • liver

inspection - assessment

• petechiae - pinpoint hemorrhages skin/mucosal

• nosebleeds

• ecchymosis (bruising) - large areas of hemorrhage into skin

diagnostic testing

• biopsy of bone marrow/lymph node

• analysis of blood cells

• special test for specific diseases

biopsy of bone marrow/lymph node - diagnostic testing

• bone marrow = dx hematopoietic cancers + other diseases

• lymph = ± lymphoma

analysis of blood cells - diagnostic testing

• Hct, Hgb, RBC blood smears = presence/absence of anemia

• low = anemia

• Hct = volume of RBC to % of blood volume (g/dL)

• RBC = cells in small chamber/cubic mm

• size/Hb concentration = microscope

• WBC % + platelet count

• retic count = % immature RBC

  • >2% = increase production of RBC

special test for specific diseases - diagnostic testing

• Hgb electrophoresis = genetic abnormalities of Hgb

• serum ferritin - indirect measure Fe stores

• flow cytometry = determine diseases result of antibodies against RBC/WBC

hemostasis

• prevents excessive bleeding after injury

• interaction of

  • blood vessels

  • platelets

  • chemical coagulation factors in plasma

endothelial injury - whats happening?

• blood vessels undergo spastic contraction

• blood shunted to non-injured vessels

• platelets

  • physically obstruct BF

  • promote vasoconstriction

  • release chemical = further hemostatic process

  • fibrinogen → fibrin monomer

    • polymerizes = thrombus = clotting cascade (from liver)

  • inhibitors slow rxn

  • cascade designated by roman numerals

coagulation cascade

• thrombosis

  • formation of blood clot through interaction of tissue, platelets, plasma proteins = coagulation factors

• fibrin formation

  • enzymatic steps = coagulation/clotting cascade

thrombus

blood clot in blood vessel caused by fibrin (polymerized to block vessel)

organized thrombus

thrombus converted into granulation tissue/scar

fibrin

fibrin monomers (plasma proteins) bind = form stringy, strong, insoluble protein (mesh)

plasmin

breaks down insoluble fibrin clot into soluble fragments during repair of tissue after clot formation

causes of hemorrhage

• trauma - most common

  • injury to larger vessels = sig med treatment

• spontaneous bleeding

  • platelet count <10,000/mL

  • platelets defective

• hereditary coagulation disorders

  • hemophilia

• thrombocytopenia

  • decreased # circulating platelets

  • caused by

    • bone marrow failure

    • peripheral destruction of platelets

    • temporary platelet deficiency treated with platelet transfusion

• acquired coagulation disorders

  • associated with other diseases/drugs in susceptible individuals

virchow’s triad

• conditions leading to thrombosis

• endothelial cell injury

• stasis or turbulence of blood flow

• hypercoagulable state

endothelial cell injury - virchow’s triad

• trauma

• vasculitis

• cig smoke

• radiation

• atherosclerosis (plaque arteries)

• infarction

• turbulent BF

• bacterial endotoxins

stasis/turbulence of blood flow - virchow’s triad

• bifurcation of arteries

• atherosclerosis (plaque arteries)

• aneurysm

• venous stasis (incompetent valves, bed rest)

hypercoagulable state - virchow’s triad

• increased estrogen (birth control, preg)

• trauma

• surgery

• inherited coagulopathy

• cancer

• obesity

diathesis vs coagulopathy

• hemorrhagic diathesis = tendency to bleed

• coagulopathy = abnormality in coagulation mechanism = excessive bleeding/clotting

platelet decrease/deficiency cause…

• petechiae

• epistaxis

• hematuria = blood urine

• hematochezia = blood from anus

• menorrhagia = heavy/prolonged menstrual bleeding

• increased bleeding following delivery

• hematomas = tissue bleeding

  • joints, soft tissues, brain

• purpura - large collections of blood in skin (many petechiae)

platelet count - diagnostic test

• do not ID platelet abnormalities

platelet function analyzer - diagnostic test

• PFA-100

• measure platelet dependent coagulation under flow conditions

activated partial thromboplastin time (aPTT) - diagnostic test

• test for deficiencies in intrinsic pathway of coagulation mech

prothrobin time (PT) - diagnostic test

• assess disorder of extrinsic pathway of coagulation

• expressed in International normalized ratio (INR)

fibrinogen assay - diagnostic test

• measure fibrinogen levels

• measure fibrin degradation products/d-dimer reflects fibrinolysis

hemophilia

• most common hereditary coagulation disorder

• common in 2 forms of X genes = affecting males

• females = 2 defective genes to manifest = less common

• hemophilia A

• hemophilia B

• dx = coag factor defect (Plt ct, aPTT, PT), factors VIII and IX

hemophilia A

• classic

• deficiency of factor VIII

hemophilia B

• christmas disease

• 20% NOT hereditary = new mutants

• deficiency of factor IX

• bleeding joints, muscles, soft tissues

• bleed excessively from minor injury/surgery

spontaneous thrombosis

• rare hereditary deficiencies of

  • antithrombin III

  • protein C

  • protein S

The factor V Leiden mutation - spontaneous thrombosis

• coagulant factors increased after trauma, operations, childbirth

• Pathogenesis

  • small thrombi > obstruction of blood flow > ischemic injury to tissue supplied by that vessel

infarct - Spontaneous thrombosis

• large thrombi in larger arteries, though may not cause complete blockage, can be pathological if bits of thrombi (called EMBOLI) is chipped off it, and travel in the blood stream, causing INFARCTS

• Cerebral infarct - stroke

• Myocardial Infact - heart attack

• Splenic infarct - Spleen

• Renal infact - Kidney

• Pulmonary embolism - Lungs

coagulation modifier drugs

• anticoagulants

• antiplatelets

• thrombolytics

• antifibrinolytics

anticoagulants

• warfarin sodium (PO)

• unfractionated heparin, low-molecular weight heparin = Enoxaparin (SC)

• argatroban, bivalirudin, dabigatran etexilate mesylate

• fondaparinux rivaroxaban

warfarin sodium (PO)

• anticoagulant

• subclass = coumadin

• MOA = inhibits vit k-dependent clotting factors

• Indi = atrial fibrillation, thrombus prevention, prosthetic heart valve

• Contra = allergy, acute bleeding, thrombocytopenia, preg

• AE = bleeding, thethargy, muscle pain, purple toes

• Nursing = VS, s/s of bleeding, PT/INR, natural health products (result in increased bleeding (dong quai, garlic, ginkgo, st john wort))

• TA

  • onset = 24-72hrs

  • half-life = 0.4-3 days

  • [peak plasma] = 4hrs

  • duration of action = 2-5 days

• NOTE = dose cut in half

  • inhibits vit-k dependent clot factors, foods high in vit k may reduce warfarin ability to prevent clots

    • leafy greens = food-drug interaction

    • maintenance warfarin dose established = eat greens, but consistent with intake (affect INR)

unfractionated heparin, low-molecular weight heparin = Enoxaparin (SC)

• anticoagulant

• subclass = heparins

• MOA =LMWH - greater affinity factor Xa

• Indi = thromboprophylaxis in surgery, higher dose in DVT/PE treatment

• Contra = LMWH - indwelling epidural catheter (given 2hrs after removed)

• AE = bleeding, hematoma, nausea, anemia, thrombocytopenia, fever, edema

• Nursing = ensure Heparin + LMWH ordered at same time

• TA =

  • LMWH: Onset: 3-5 hrs Half-life: 4-5 H

    Peak Plasma Conc: 4-5 H 

    Duration of action: 12 H

    Heparin: Onset: 20-30min Half-life: 1-2 H

    Peak Plasma Conc: 2-4 H 

    Duration of action: 8-12 H

argatroban, bivalirudin, dabigatran etexilate mesylate

• anticoagulant

• subclass = Direct Thrombin Inhibitors

• MOA = PO - prevent stroke/thrombosis

• Indi = non-valcular atrial fibrillation

• AE = bleeding, dizzy, SOB, fever, urticaria (hives)

• Nursing = NO antidote, no BW monitoring, s/s bleeding

• TA

  • onset = 24-72hrs

  • half-life = 0.4-3

  • [peak plasma] = 4hrs

  • duration of action = 2-5 days

• NOTE = activated in liver, reversibly binds to free and clot-bound thrombin

  • excreted in kidneys = dose dependent on kidney function

  • normal does = 150mg BID, reduced to 75mg DIB if creatine clearance <30mL/min

fondaparinux rivaroxaban

• anticoagulant

• subclass = Selective Factor Xa Inhibitors

• Indi = DVT or pulmonary Edema

• Contra = allergy, creatinine clearance of less than 30/min or body wt <50kg

• AE = bleeding, hematoma, dizzy, rash, GI, distress, anemia, thrombocytopenia

• Nursing = NO antidote

• TA

  • onset = 2hrs

  • half-life = 17-21 hrs

  • [peak plasma] = 2-3hrs

  • duration of action = 24hrs

antiplatelets

• Aspirin (PO)

• eptifibatide (Integrilin)

• Clopidogrel

Aspirin (PO)

• antiplatelet

• subclass = Salicylate antiplatelet

• MOA = acetylates/inhibits cyclooxygenase in platelet irreversibly so platelet cannot regenerate enzymes

• Indi = stoke prevention, dual anti-platelet therapy

• Contra = allergy, thrombocytopenia, active bleeding, leukemia, trauma, GI ulcer vi K deficiency, recent stroke

• AE = drowsy, dizzy, confusion, flushing, N/V, GI bleeding, thrombocytopenia, agranulocytosis, leukopenia, neutropenia, hemolytic, anemia, bleeding

• Nursing = VS, s/s bleeding, PT/INR, natural health products (result in increased bleeding (dong quai, garlic, ginkgo, st john wort))

• TA

  • onset = 15-30 min

  • half-life = 2-3hrs

  • [peak plasma] = 0.25 - 2 hrs

  • duration action = 4-6 hrs

eptifibatide (Integrilin)

• antiplatelet

• subclass = GP Iib/Iiia inhibitors

• MOA = block receptor protein by name that occurs in the platelet wall membranes

• Indi = acute unstable angina and MI, endovascular procedure, coronary angioplasty

• Contra = allergy, thrombocytopenia, active bleeding, leukemia, trauma, GI ulcer vi K deficiency, recent stroke

• AE = bradycardia, hypotension, edema, dizzy, bleeding, thrombocytopenia

• Nursing = ensure Heparin and LMWH NOT ordered at same time

• TA

  • onst = 1 hr

  • half-life = 2-2.5hrs

  • duration action = 4hrs

Clopidogrel

• antiplatelet

• subclass = ADP inhibitor

• MOA = inhibits platelet aggregation by altering platelet membrane = no longer receive signal to aggregate/form clot

• Indi = reduce risk of fetal/nonfatal thrombotic stroke, prophylaxis of transient ischemic attacks (TIAs), post MI prevention of thrombosis

• Contra = allergy, thrombocytopenia, active bleeding, leukemia, trauma, GI ulcer vi K deficiency, recent stroke

• AE = chest pain, edema, flu s/s, headache, dizzy, fatigue, abdo pain, diarrhea, nausea, epistaxis, rash, pruritus

• Nursing = NO antidote, no BW monitoring, monitor for s/s bleeding

• TA

  • onset = 1-2 hrs

  • half-life = 8hrs

  • [peak plasma] = 1hr

  • duration action = 7-10 days

thrombolytics

• Alteplase (Activase)

• Tenecteplase (TNKase)

• NOTE = substances that form clots destroyed by plasmin

• mimic body own process of clot destruction

Alteplase (Activase)

• Thrombolytics

• subclass = t-PA

• MOA = activates conversion of plasminogen to plasmin = breaks down/lyse thrombus

• Indi = acute MI, arterial thrombosis, DVT, occlusion of sunts/catheters, PE, acute ischemic stroke

• Contra = drug allergy, concurrent drugs that alter clotting, hx of surgery, trauma, bleeding

• AE = internal/intracranial/superficial bleeding, hypersensitivity, anaphylactoid rxn, N/V, hypotension, cardiac dysrhythmias

• Nursing = VS, s/s bleeding

• TA

  • onset = intermideiat

  • half-life = 5 min

  • [peak plasma] = 60 min

  • duration action = depends on duration of infusion

Tenecteplase (TNKase)

• Thrombolytics

• subclass = t-PA

• MOA = activates conversion of plasminogen to plasmin = breaks down/lyse thrombus

• Indi = lysis of suspected occlusive coronary artery thrombi with MI specific to TNK + indications for Alteplase

• Contra = drug allergy, concurrent drugs that alter clotting, hx of surgery, trauma, bleeding

• AE = internal/intracranial/superficial bleeding, hypersensitivity, anaphylactoid rxn, N/V, hypotension, cardiac dysrhythmias

• Nursing = VS, s/s bleeding

antifibrinolytics

• Aprotinin (Artiss Trasylol)

• tranexamic acid (Cyklokapron)

• desmopressin acetate (DDAVP) - injectables, PO, intranasal

• NOTE = all prevent lysis of fibrin

  • fibrin = help platelet plug insoluble and anchors clot to the damaged blood vessel

  • drug PROMOTE clot formation = hemostatic drugs = OPPOSITE anticoagulants (prevent clot formation)

Aprotinin (Artiss Trasylol)

• antifibrinolytic

• subclass = Natural antifibrinolytic

• MOA = inhibits proteolytic enzyme trypsin, plasmin, kallikrein which lyses proteins that destroy fibrin clots. inhibiting enzymes = aprotinin prevent degradation of fibrin clot + inhibit action of complement systems

• Indi = prevention/treat excessive bleeding from systemic hyperfibrinolysis/surgical complication

• Contra = allergy, disseminated intravascular coagulation (DIC)

• AE = dysrhythmias, ortho hypo, bradycardia, headache, dizzy, fatigues, hallucinations, convulsions, N/V, abdo cramp, diarrhea

• Nursing = assessment, VS, s/s bleeding in skin/oral mucosa/gums/urine/stool, PTT, PT, INR

• TA

  • onset = 15-30 min

  • half life = 2-3hrs

  • [peak plasma] = 0.25-4hrs

  • duration action = 4-6hrs

tranexamic acid (Cyklokapron)

• antifibrinolytic

• subclass = Synthetic Antifibrinolytic

• MOA =reversible complex with plasminogen + plasmin = ind tp lysine site of plasminogen, tranexamic acid displeased plasminogen from surface of fibrinin = prevent plasma from lysing fibrin clot = ONLY WORK IF CLOT FORMED

• Indi = prevention/treat excessive bleeding from systemic hyperfibrinolysis/surgical complication

• Contra = allergy, disseminated intravascular coagulation (DIC)

• AE = dysrhythmias, ortho hypo, bradycardia, headache, dizzy, fatigues, hallucinations, convulsions, N/V, abdo cramp, diarrhea

• Nursing = assessment, VS, s/s bleeding in skin/oral mucosa/gums/urine/stool, PTT, PT, INR

• TA

  • onset = 1hr

  • half-life = 2-2.5hrs

  • duration action = 4hrs

desmopressin acetate (DDAVP) - injectables, PO, intranasal

• antifibrinolytic

• subclass = Synthetic Antifibrinolytic

• MOA = increasing Willebrand factor (anchodrs platelets to damaged velsselvvia GP Ilb platelet receptor)

• Indi = surgical/postoperative homeostasis + management of bleeding in pt with hemophilia A or type I Willebrand disease

• Contra = allergy, disseminated intravascular coagulation (DIC) + nephrogenic diabetes insipidus

• AE = dysrhythmias, ortho hypo, bradycardia, headache, dizzy, fatigues, hallucinations, convulsions, N/V, abdo cramp, diarrhea

• Nursing = assessment, VS, s/s bleeding in skin/oral mucosa/gums/urine/stool, PTT, PT, INR

• TA

  • onset = 1-2hr

  • half-life = 8hrs

  • [peak plasma]= 1hr

  • duration action = 7-10 days

24yr pt MVA = above knee aputation + bedridden 2wks. pt has TROUBLE BREATHING. pt developed…?

• pulmonary embolism

  • Virchow’s triad

  • pt injured

  • stasis of blood b/c bedridden

  • hypercoagulability b/c surgery

• pt high risk for thrombus formation

  • deox blood flow to small arteries in pulmonary system (blocked by thrombus) = ineffective O2 exchange = less O2 in blood = SOB

24yr pt MVA = above knee aputation + bedridden 2wks. pt has TROUBLE BREATHING = Pulmonary Embolism. what coagulation modifier + adverse rxn?

• drug = Alteplase (Activase) (Thrombolytic)

• AE = internal/intracranial/superficial bleeding, hypersensitivity, anaphylactoid rxn, N/V, hypotension, dysrhythmias

disorders of WBC

• blood infections

• blood cancers

• NOTE = secondary effects of other diseases generally

  • most infections cause leukocytosis (increase # WBC)

blood infection - disorders of WBC

• malaria

  • endemic (Americas, Asia, Africa) kills 1-3 mil/yr

  • parasite causes infects/destroys RBC

• HIV

  • pandemic, 3mil/yr

  • infects lymphocytes/destroys rate faster than replaced

  • pt die from infection

blood cancers - disorders of WBC

• leukemia

  • cancer of WBC

  • subclassified to particular lineage involved

• lymphoma

  • WBC cancer via involvement of sites OTHER THAN bone marrow/blood

• multiple myeloma

  • cancer of plasma cells

leukemia - neoplasm

• WBC disorder

  • NO TUMOR
    interspersed in lymphatic/circulatory system = interfere with normal function

• malignant WBC neoplasms that

  • originate/spread diffusely in BONE MARROW

  • produce high WBC in PERIPHERAL blood

• classified via

  • type of WBC

  • chronicity of disease

• degree of differentiation relates to duration

  • acute = poorly differentiated cells = rapid course

  • chronic = well-differentiation = slow course

• dx via blood smear/bone marrow exam

acute lymphocytic leukemia (ALL)

• most common childhood leukemia

• rapidly fatal unless treated aggressively

• successful therapy = long-term survival and cure

chronic lymphocytic leukemia (CLL)

• older adults

• prolonged course

diagnostics of leukemia

• blood smear

• bone marrow exam

treatments of leukemia

• chemo

• radiation

• bone marrow transplant

manifestations of leukemia

• weakness

• anemia

• bleeding

• infection

• leukemic cells in blood/bone marrow

lymphoma - neoplasm

• several types of malignant neoplasms of lymphocytes + histiocytes

• originated in lymphoid tissues OUTSIDE of bone marrow

• produce mass lesions

• DO NO release malignant cells into blood

• class = cell type

  • Hodgkin = Reed-Sternberg cell

• non-Hodgkin

  • cell size

  • immunologic markers

  • histological pattern

  • details of cell structure

cancer treatment

• surgery

• radiation

• targeted drug therapy

• biologic therapy

• chemo (antineoplastic agents)

  • cell-cycle nonspecific drugs = cytotoxic (cell kill at ANY phase)

  • cell-cycle specific drugs = cytotoxic during SPECIFIC cell cycle

cancer drugs (TI/AE)

• LOW therapeutic index (TI)

• AE = rapidly dividing cells

  • hair follicle = hair loss

  • GI tract = N/V = EMETIC POTENTIAL

  • bone marrow = toxicity

  • fertility reduction in postpubertal age

• CANNOT discriminate against normal/cancer cells

• if GI/Bone marrow effects = NO increase dose

• contraindications

  • weakened stat of pt

  • low WBC, infection, nutritional comp, dehydration, decrease liver/kidney function

antineoplastics

• class = cell cycle non-specific

• MOA = cytotoxic ANY phase

• Indi = part of complex, frequent revision by oncology, low TI

• Contra = preg, liver disease (HBV/HCV)

• AE = hair loss, N/V, bone marrow toxicity

• Nursing = VS, bloodwork, preg test reproductive age

• TA

  • [peak plasma] = 1-4hrs

pain management/transfusion - antineoplastics

• class = cell cycle-specific

• MOA = cytotoxic at SPECIFIC cell cycle phase

• Indi = part of complex, frequent revision by oncology, low TI

• AE = hair loss, N/V, myelosuppression (decreased RBC production from bone marrow), diarrhea, toxicity

• Nursing = VS, blood work, PE, nut/hydration