Anemia, Cytopenias and thrombosis Oxford

Question 1

List symptoms of anemia (acute and chronic)

Answer 1

Acute:

• tachycardia
• orthostatic hypotension
• dyspnea

Chronic (compensation by increasing plasma volume, shifting hemoglobin dissociation curve)

• fatigue
• decreased exercise capacity
• decreased appetite
• dizziness
• vertigo
• syncope
• tinnitus
• impaired cognitive function
  *

Question 2

List causes of anemia in palliative care

Answer 2

• bone marrow infiltration
• blood loss
• hemolysis
• anemia of chronic disease
• myelosuppression from chemotherapy
• myelodysplasia from treatment
• folate deficiency from malnutrition
• GI resections

Question 3

Anemia of Chronic Disease: pathophysiology

Answer 3

• hypoproliferative anemia
• immunological reaction to the presence of inflammation and malignancy
• cytokines and monocytes release (INFy, TNFa, IL6, IL10)
  
  • stimulate uptake into and storage of iron in macrophages and monocytes
  • prevent export of iron out
  • suppress ability of kidneys to make erythropoeitin
  • damage red cell membranes
  • prevent differentiation and proliferation of red cell progenitors in marrow
• hepcidin
  
  • retains iron in Reticulendothelial system

Question 4

Anemia of Chronic Disease: diagnosis

Answer 4

• Diagnosis of exclusion
• normocytic, normochromic
• mild to moderate (80-95 g/L)
• Reticulocyte count low (reduced marrow output)
• Serum iron, TIBC, iron saturation LOW
• Ferritin normal or elevated
  
  • ferritin = total body iron storage. Iron in RES abdundant, therefore ferritin normal or high in ACD

Question 5

Acute and Chronic Hemorrhage: Anemia

Answer 5

• GI, head and neck, lung, uterine, urinary cancers - common
• sarcomas, hepatomas, melanomas, ovarian cancers - common
• severe iron deficiency
• microcytic, hypochromic red cells
• target cells, pencil cells

Question 6

Iron supplementation

Answer 6

• oral route preferred
• 150-200 mg elemental iron /day
• SE: nausea, heartburn, constipation (change formulations, reduce dose)
• Parenteral iron : malabsorption or quick loss
  
  • dose of iron (Mg) = whole blood hemoglobin deficit (g/dL) x body weight (lb)
  • Iron sucrose 20 mg elemental iron / ml
    
    • hypotension, cramps, nausea, headache, vomiting, diarrhea
  • Iron dextran 50 mg elemental iron/ml
    
    • severe anaphylaxis <1%

Question 7

Nutritional deficiencies in Anemia

Answer 7

• B12- similar to elderly populaton
• Folate deficiency (hematopoeisis)
  
  • megaloblastic anemia (< 5 ug folic acid intake x 4 months)
  • folic acid absored in jejunum, duodenum (resections - low absorption)
  • large red cells, RCV increased, hypersegmented neutrophils
  • anemia, thrombocytopenia, neutropenia
  • oral replacement 1-5 g/day

Question 8

Anemia: Bone marrow infiltration

Answer 8

• Most common breast, lung, prostate metastasize to marrow
• leucoerythroblastic picture:
  
  • immature nucleated red cells
  • myeoloid white cell precursors
  • teardrop red cells
• anemia, elevated WBC, platelets low, high, normal
• Bone marrow failure hematological malignancies
  
  • pancytopenia
• Thrombocytopenia:
  
  • spontaneous bleeding < 20x 10(9)
  • ICH < 5x 10(9)

Question 9

Neutropenia

Answer 9

• myelodysplasia/suppression from chemotherapy
• marrow infilatration from
• intrinsic bone marrow failure
• ANC < 1500 cells/ml, severe < 500 cells/ml
• febrile neutropenia:
  
  • single oral temp > 38.3 or > 38 for more than 1 hour
  • severe risk: comorbidities, liver, renal dysfunction
  • Fluoroquinolone prophlylaxis ANC < 100 and afebrile
• Febrile neutropenia
  
  • CBC with differential, CH6, Cr, hepatic enzymes, total bili,
  • 2 sets blood cultures
  • CXray
  • Urine
• Febrile neutropenia treatment:
  
  • anti-pseudomonal beta lactam (meropenem, pip-tazo)
  • Vanco (catheter infection, skin, soft tissue, pna)

Question 10

DIC

Answer 10

• overproducton procoagulants generates intravascular microthrombi
• ischemic MOF/ clotting + increased bleeding
• Acute vs chronic
• risk:
  
  • advanced age, advanced cancer, chemotherapy, anti-estrogen therapy
  • sepsis, immobilization, liver mets
  • Adenocarcinoma : tendency towards thrombosis
• D-dimer HIGH
• Platelets LOW
• INR HIGH / PTT HIGH
• Fibrinogen LOW
  
  • fibrinogen acute phase reactant so can be normal.

Treatment:

• cryoprecipitate (factor VIII and fibrinogen)
• FFP
• platelet transfusions

Question 11

Transfusions in Palliative Care

Answer 11

• Red cell transfusion
  
  • < 70 g/L if no bleeding
  • symptomatic treatment of fatigue and dyspnea if aligned with goals
  • Cochrane review : subjective improvement
  • No good data
• Platelet transfusion
  
  • > 50,000 / uL - unlikely bleeding
  • < 10,000 /uL - high risk spontaneous bleeding, consider prophlyactic transfusion
  • short duration of transfusion (days?)

Question 12

Tranfusion reactions / adverse events

Answer 12

• transmission of blood borne illness
• Tranfusion reactions:
  
  • Acute intravascular hemolytic (ABO incompatability)
    
    • fever, tachycardia, hemoglobinuria, shock, dyspnea, hypotension
  • Acute extravascular hemolytic
  • Febrile non hemolytic (tylenol, hydrocortisone)
  • Mild allergic reactions (1%)
    
    • benadryl, stop infusion, then re-initiate transfusion
  • Anaphylaxis
  • Transfusion associated circulator overload (TACO)
    
    • slow tranfusion, lasix
  • Septic
  • Transfusion related acute lung injury (TRALI)

Question 13

Erythropoetin Stimulants

Answer 13

• Erythropoeitin produced by kidney, growth factor for red cell progenitors in bone marrow.
• epoeitin and darbopoeitin
• reduces need for red cell transfusions in cancer patients on myelosuppressive chemotherapy
• Recommendatsion by American Society of Hematology/Clinical Oncology
  
  • Hg < 100 g/L and on myelosuppressive chemotherapy

Question 14

VTE : etiologies

Answer 14

Virchow’s triad:

• venous stasis
  
  • lymphandepathy, tumour compression, SCC, immbolity
• endothelial injury
  
  • chemotherapy, surgical interventions, CVC access
• hypercoagulability
  
  • malignancy procoagulant changes

Question 15

Goals of VTE treatment

Answer 15

Short Term

• decreasing symptoms
• preventing clot extension
• preventing embolic events
• preventing early recurrence
• decreasing mortality

Long Term

• decreasing risk of recurrence
• reducing post thrombotic symptoms

Question 16

VTE treatment in palliative care

Answer 16

• LMWH
• Warfarin - oxford
• NOAC - not covered in oxford
• Must consider in palliative care
  
  • hospitalization for initial treatment
  • symptom management
  • burden of treatment (injections)