Hematology Treatment Guidelines

Timothy Beer
I) RBC Disorders and Anemias
Cold Agglutinin Disease (Cold AIHA)
All Patients
Avoid cold weather (stay warm)
* NOT responsive to prednisone or splenectomy

G6PD Deficiency
Prevention of hemolytic events
Avoidance of oxidative stress (certain drugs, fava beans)

Hereditary Spherocytosis
Anaplastic crises
Transfusion
Moderate-to-severe hereditary spherocytosis (all but the mildest cases)
Splenectomy (curative)
* Give polyvalent vaccine prior to splenectomy to prevent infection by encapsulated organisms (e.g. pneumococci)

Prophylaxis against megaloblastic anemic crises

Oral folic acid supplements
* These patients are at increased risk for megaloblastic anemia due to increased erythropoiesis (and thus folate use)

Iron deficiency anemia

All Patients
Oral inorganic ferrous iron (Fe2+)
* Continue for many months until iron stores are replenished
* Take on empty stomach, separate from meals

Patients with malabsorption or chronic blood loss exceeding gut absorptive capacity
IV iron
* Continue for many months until iron stores are replenished
* May cause serious anaphylactic allergic reaction
* Several IV formulations are available

Megaloblastic Anemia: B12 Deficiency

Initial repletion of B12
Step 1: IM 1000µg B12/day for 1 week
Step 2: IM 1000µg B12/week for 1 month
Step 3: IM 1000ug B12/month indefinitely
* WARNING: risk of HYPOKALEMIA in megaloblastic anemic patients during repletion therapy
* Do NOT treat B12-deficient patients with folate (may worsen neurological symptoms)
* These guidelines vary widely, so it would be worthless to memorize them

Maintenance of B12 stores after initial repletion

Oral 1000-2000ug B12 daily for life
* Do NOT treat B12-deficient patients with folate (may worsen neurological symptoms)

Megaloblastic Anemia: Folate & B12 Deficiency

Folate deficiency patients in which B12 deficiency is even remotely possibly present
Step 1: B12 repletion
Step 2: Folate repletion
* Do NOT treat with folate alone or with folate before B12
* If patient has B12 deficiency, giving folate alone may WORSEN NEUROLOGICAL symptoms

Megaloblastic Anemia: Folate Deficiency

Secondary to a permanent condition
Oral folic acid supplements 1-5 mg daily for life
* Make SURE the patient does NOT have B12 deficiency before treating with folate

Secondary to a temporary condition

Oral folic acid supplements 1-5 mg daily until replete
* Make SURE the patient does NOT have B12 deficiency before treating with folate
 Hematology Treatment Guidelines
Timothy Beer
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Long-term supportive management
1) Anti-coagulation (to prevent thrombosis)
2) Iron supplementation (if there is iron deficiency)
3) Transfusions (for anemia)
Reduction of need for transfusions and improved quality of life
Eculizumab (monoclonal antibodies to compliment C5)
* Eculizumab reduces intravascular hemolysis (but is not curative)

Pyruvate Kinase Deficiency

Subset of patients who experience hemolysis significant enough to require transfusion
Splenectomy (not curative, but reduces transfusions)
* Most patients with PK deficiency will NOT require splenectomy
* Although splenectomy does not completely stop hemolysis, it lowers it to a sub-clinical (asymptomatic) level

Warm Autoimmune Hemolytic Anemia (AIHA)

All Patients
1st line: corticosteroids (prednisone)
If prednisone fails: splenectomy
If splenectomy fails: immunosuppresive drugs

α-Thalassemia Hemoglobin H disease

All Patients
Iron level monitoring
* These patients can have significant iron accumulation even without transfusions

During times of great stress

Transfusion

β-Thalassemia major (Cooley’s anemia)

All Patients
1) Transfusions (every 3 weeks)
2) Iron chelation to prevent iron overload (e.g. deferoxamine)
* Iron buildup results from chronic transfusions and increased intestinal absorption to support hyperactive bone marrow
* If iron accumulation causes significant splenomegaly, splenectomy may be indicated

Patients with very severe disease who have identified a matched bone marrow donor
Bone marrow transplant (curative)
* Requires matched bone marrow donor
* Better transplant outcomes occur in very young patients without excessive iron accumulation

II) Platelet Disorders

Thombotic Thrombocytopenic Purpura (TTP)
Patients with less common congenital form (absent ADAMTS13 production)
Plasma infusion
* Also provide full-fledged supportive care

Patients with more common acquired form (antibody against ADAMTS13)

Plasma exchange
* Also provide full-fledged supportive care
 Hematology Treatment Guidelines
Timothy Beer
III) Coagulation Disorders
Disseminated Intravascular Coagulation (DIC)
All Patients
Treat underlying cause
Interruption of clotting process if patient is thrombotic or if replacement therapy fails
Heparin
* Use of heparin for DIC is somewhat controversial and is a measure of last resort

Patients with severe depletion of platelets, fibrinogen or clotting factors

Transfusion of platelets, FFP and cryoprecipitate

Hemophilia A (factor VIII deficiency)

Prophylaxis for mild disease
Desmopressin (ddAVP)
* Increases levels of endogenous VIII in patients with > 5% baseline levels

Prophylaxis for moderate-to-severe disease

Recombinant factor VIII
* ddAVP will NOT do any good in these patients (they have too little endogenous VIII to work with)

Treatment of bleeding episodes

Recombinant factor VIII
* 30-50% for normal bleeding, 100% for CNS and other surgeries

Hemophilia B (factor IX deficiency)

Major bleeding episode
Recombinant factor IX or purified factor IX concentrates
* Doses of recombinant IX for hemophilia B are 2x those used for VIII for hemophilia A

Minor bleeding episode

Plasma transfusion

Hemophilia C (factor XI deficiency)

All Patients
Fresh frozen plasma (FFP)

Liver Disease-related Coagulopathies

All Patients
Fresh frozen plasma (FFP)
* FFP contains all coagulation factor zymogens, vWF multimers, fibrolytic control proteins, plasminogen, anticoagulants

The minority of patients who have active bleeding or moderate-severe thrombocytopenia

Platelet transfusions
* Platelets are given in addition to, not instead of, FFP

Vitamin K Deficiency
All Patients
Vitamin K (oral or IV)
* Do NOT give vitamin K via SQ or IM

von Willebrand Disease (vWD)

All Patients
1) vWF-factor VIII concentrates (all types)
2) ddAVP (type 1)
* Additional therapies as needed include cryoprecipitate, FFP, estrogens (for menorrhagia) and anti-fibrinolytics
 Hematology Treatment Guidelines
Timothy Beer
Warfarin excess
Elevated INR + bleeding
1) Withhold warfarin
2) Give Vitamin K (oral or IV)
3) Consider FPP or prothrombin concentrate complexes (PCC)
Elevated INR, but NO bleeding
Withhold warfarin
* May or may not wish to give vitamin K as well

IV) Thrombotic Disorders

DVT/PE
Current mild-moderate DVT/PE
1) Heparin or LMWH
2) Warfarin
* Start Heparin or LMWH immediately; start warfarin within 24 hours
* Heparin requires aPTT monitoring, warfarin requires INR/PT monitoring, LMWH requires good renal function

Surgical prophylaxis
Warfarin or LMWH
* If warfarin, start night before surgery and continue for 4-6 weeks
* If LMWH, start within 6-24 hours post-surgery and continue for 2-6 weeks

V) Stem Cell Disorders

Aplastic Anemia
All Patients
Three main components:
1st: withdraw any known or suspected offending agents
2nd: platelet and RBC transfusions + antibiotics
3rd: immunosuppressive therapy and/or allogenic marrow transplant
* Immunosuppressive therapy used for idiopathic disease
* Immunosuppressive agents typically used are anti-thymotic globulin + cyclosporine
* Similar outcomes for immunosuppresive therapy for old and young patients (with idiopathic disease)

Myelodysplastic syndromes (MDS)

High risk or INT-2 MDS
Azacitidine
* Prolongs disease-free survival
* Delays onset of leukemic transformation and death

Low risk or INT-1 MDS (especially with 5q-)

Lenalidomide
* Induces erythroid responses
* Induces complete cytogenic remissions (50% of patients)

VI) Myeloproliferative Disorders

Essential Thrombocytopenia
All Patients
Decrease platelet count or inhibit platelets with at least one of following:
1) Aspirin
2) Hydroxyurea
3) Anagrelide
4) Plateletpheresis (rarely)
 Hematology Treatment Guidelines
Timothy Beer
Polycythemia Vera
All Patients
1) Phlebotomy (to decrease blood viscosity and keep HCT < 45%)
2) Hydroxyurea (to decreases bone marrow proliferation)
3) Low dose aspirin (as anti-thrombotic prophylaxis)
4) JAK-2 inhibitors
* Almost all polycythemia vera patients have JAK-2 mutation

Primary Myelofibrosis
All Patients
Supportive therapy
1) Hydroxyurea (but not very well tolerated)
2) Transfusion
3) Splenectomy
4) JAK2 inhibitors
* Not all primary myelofibrosis patients have JAK-2 mutation

Young patients (there are very few)

Allogenic stem cell transplant (curative)

VII) Hematologic Malignancies

Chronic Myeloid Leukemia
Philadelphia chromosome t(9;22)-positive patients (>90%)
Imatinib (Gleevec)

Follicular Lymphoma
1st line therapy for all patients with symptomatic disease
Combination chemotherapy (e.g. CHOP)
* Combination chemotherapy is very effective, but patients will eventually relapse

2nd line therapy for patients who are young enough

Bone marrow transplant (curative)

Hairy Cell Leukemia

All Patients
Purine analogs (Cladribine, Pentostatin)
* Extremely good prognosis with treatment (regardless of degree of symptoms at presentation)

Hodgkin Lymphoma
All but earliest disease
Chemotherapy (ABVD)
* ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine
* Cures vast majority
* Given on outpatient basis

Earliest disease (stage I-II)

Radiation
* Cures 90%

VIII) Other
Heparin-induced Thrombocytopenia (HIT)
All Patients
1) Stop heparin
2) Start direct thrombin inhibitor (lepriudin, argatroban, bivalirudin)

Hypereosinophilic syndrome
All Patients
Steroids and/or chemotherapy
 Hematology Treatment Guidelines
Timothy Beer
Iron overload
Secondary to hereditary hemochromotosis
Phlebotomy
Secondary to prolonged red cell transfusions in chronic anemia
Iron chelation