Myeloproliferative Disorders Flashcards
Too Many Red Cells
Polycythemia vera (PCV)
Too Many Platelets
Essential Thrombocytosis (ET)
Too Many Neutrophils
Chronic Myelogenous or Chronic Myeloid Leukemia (CML)
Myeloproliferative Syndromes
Symptoms?
Clonal Disorders of Blood Cells that would fall into the Neoplastic Spectrum
Fatigue, Abdominal Discomfort, Itching or Profuse Sweating
Generally Associated with Splenomegaly
Extra-medullary Hematopoiesis is Common
Disease Control for Many Years is Common
Cure is Not Possible at this Time
Polycythemia vera (PCV) Labs
Elevated RBC Mass Associated with a Mild Increase in WBCs and Platelets
Incidence 2/100,000 – 18/100,000 adults.
Incidence increases with increasing age.
Janus Kinase 2 (JAK2) plays a key role
symptoms of Polycythemia vera
Fatigue, headache, puritis (itching), flushing, abdominal discomfort due to splenomegaly.
Less common Sx: TIA, Retinal arterial occlusion, mesenteric or hepatic venous thrombosis or arterial thrombosis in a variety of organs.
Other Sx: Epistaxis, easy bruising, digital ischemia
2 things that are found on physical exam suggesting polycythemia vera?
Ruddy complexion
Mild splenomegaly
How to diagnose polycythemia vera?
When there is significant mature erythrocytosis (Hct > 60%) with some modest increase in mature platelets and neutrophils
The WBC & Platelets will be Normal and Hct > 52% in males or > 48% in females, but < 60%.
what are the definitive tests that are hard to obtain in the field for polycythemia vera?
are those of Total Body Plasma Volume and Total Body RBC Volume or Mass.
What are the tests that will be normal/ low or elevated in polycythemia vera?
Serum Erythropoietin Levels ( should be low)
Splenic Ultrasound: May show splenomegaly
Fe/TIBC (should be normal), B12 ( Should be normal but may be elevated). Folate Levels (should be normal)
Test Peripheral Blood for JAK2 mutation
near normal HCT
decreased MCV
P. Vera prognosis?
Most patients with P. vera will live for many years with their disease.
most patients with P. vera will evolve into an End Stage Picture of Myelofibrosis with myeloid metaplasia.
**ultimately this condition is fatal.
Treatment for PCV
Lower Hct to Avoid Symptoms d/t increased Whole Blood Viscosity.
The Simplest & Safest Way to Do this is to Phlebotomize the Patient with PVC till they are Fe Deficient.
Chemotherpeutic drugs
Anagrelide
Jakifi
Essential Thrombocytosis (ET) platelet count is what?
Platelet Count > ~600 x 103/ mm3 Without Other Etiologies (WHO)
4 Other Etiologies to Be Excluded from ET?
Fe Deficiency
Co-existent Infectious or Inflammatory Processes
Bleeding
Other Myeloproliferative Disorders
Signs and symptoms for essential thrombcytosis?
Tends to be more common in Females
Headache &/or Dizziness. Rarely TIAs
Occasionally Easy Bruising or Small Vessel Thrombi
Occasionally Bruising & GI Bleeding
Physical Exam is usually Normal (Mild Splenomegaly may be present)
What are the laboratory findings associated with essential thrombocytosis?
Hgb & Hct should be Normal
WBC may be slightly elevated with Normal Differential
Platelet Must Be & Some Giant Platelets are Expected
JAK2 V617F may be present
R/O Chronic Myelogenous Leukemia
Normal Fe/TIBC; Normal Ferritin; Normal Sedimentation Rate (Sed. Rate)
What can elevated platelet levels effect?
spurious increase K+ on Routine Chem Profile due to Release or K+ from Platelets when the Clot Forms in the Serum (Red Top) Tube
Spurious increase pO2 on ABGs due to the Hypermetabolic State in the ABG Syringe if not quickly Cooled and put on Ice.
Treatment of Essential Thombocytosis?
treatment is based on symptoms
Observation–asymptomatic
The Patient should be Cautioned About Sx to Watch for
There should be Routine Follow-up in the absence of Sx
Most hematologists would Rx if Platelets were > 10^6
The primary Goal of Rx is to lower the Platelet Count till the Patient is Asymptomatic
Anagrelide ( Agrelin) or Hydroxyurea (Hydrea) are the Mainstays of Rx
Chronic Myelogenous Leukemia or Chronic Myeloid Leukemia (CML)
(Myeloproliferative Disorders)
an Elevated White Blood Count with the Spectrum of Immature Blood Cells Normally seen in the Bone Marrow, Now Present in the Peripheral Blood.
Thrombocytosis and Anemia are also fairly Common
Basophilia is Almost Diagnostic
Signs and symptoms of CML
Fatigue, SOB, Unexplained Weight Loss,&/or Abdominal Discomfort Due to Splenomegaly
Thrombocytosis of > 106 associated with Signs or Sx of Wet Purpura, GI Bleeding or Thrombosis Requires Urgent Treatment
Splenomegaly will be present in most patients
Must Exclude Evidence of Infection or Inflammation
What is the chronic phase of CML?
Modest Sx Mild- Moderate Splenomegaly < 5% Blasts on CBC Easily Rx’d Ph1 + Only Chromosomal Abnormality Post TKI Rx: Average Not reached at > 8 Years
Accelerated phase of CML?
increased Sx Wt Loss, Bleeding, Splenomegaly
increased WBC with10 - 20 % Blasts on CBC
Worsening Anemia
Not Responding to Conventional Rx
Multiple Cytogenetic Abnormalities
Post TKI Rx: Salvage TKI Rx 12 -18 months average
Blast phase or blast crisis of CML?
Clinical Picture Looks Like Acute Leukemia Evolving Out of CML
after TKI treatment pt has survival of ~ 6 months
Treatment of CML?
Call the Hematologist
The Goal of Rx is Complete Molecular Remission
Imatinib:
Oral TKI
Rx Recommended for Life
Late Relapses after Discontinuing Rx
Minimal Side Effects: Mild Myelosuppression, Malaise & Fatigue
Average Survival 4 years Before TKIs to»_space; 8 years on TKIs
76% Complete Cytogenetic Remission at 18 mo vs 15%
Myelofibrosis with Myeloid Metaplasia (MMM)
Clonal Disorder of the Bone Marrow characterized by increased marrow reticulum, increased marrow fibrosis, extra-medullary hematopoiesis, and splenomegaly.
how does Myelofibrosis with Myeloid Metaplasia (MMM) clinically present?
with Fatigue, Upper Abdominal Pain, and sometimes Weight Loss
GI bleed
small vessel infarcts
What are 3 signs that are common in Myelofibrosis with Myeloid Metaplasia (MMM)
Splenomegaly & Extramedullary Hematopoiesis and thrombocytosis
The Classic Picture of the MMM Peripheral Smear is what?
Leuko-erythroblastic Peripheral Smear
Treatment of Myelofibrosis with Myeloid Metaplasia (MMM)
Treatment is Primarily Supportive.
Anemia is treated with Transfusion.
Surgical Splenectomy or Irradiating the Spleen
Hydrea or Ruxolitinib (Jakafi®) Allogeneic Bone Marrow Transplantation
5 risk factors that make for a poor prognosis of MMM?
Age > 65 y.o. Constitutional Sx Hgb < 10g/dL WBC > 25 x 103/mm3 Blasts > 10%
What are not seen in Aplastic Anemia, Marrow Failure Syndromes and the Myelodysplastic Syndromes (MDS)?
Splenomegaly and Extramedullary Hematopoiesis
Aplastic Anemia, Marrow Failure Syndromes and the Myelodysplastic Syndromes (MDS)
Diseases of Primary Marrow Failure
Characterized by Cytopenias, Usually of More than One Cell Line (Pancytopenia)
Pancytopenias Associate with Cellular Marrow Secondary to Other Non Bone Marrow Etiologies
B12 &/or Folate Deficiency ETOH Poisoning Many Viral Infections Myelophthisis 20 to Cancer Late Stage MPSs with Myelofibrosis Bacterial Sepsis
Acquired or Idiopathic Aplastic Anemia (AAA) presentation?
Petechiae, Purpura, “Wet Purpura”, Pallor, & Fever are Common
Note: In the Granulocytopenic patient the traditional sign of infection, Pus, will not be present
Acquired or Idiopathic Aplastic Anemia (AAA) laboratory data
Normocytic or Macrocytic Anemia
Granulocytopenia, frequently without Lymphopenia
Thrombocytopenia
The Reticulocyte Count is Low or Zero
Hypocellular Bone Marrow with too much Fat and Little Dysplasia
Acquired or Idiopathic Aplastic Anemia (AAA) treatment
Transfusion is needed the Patient should receive Leukocyte Depleted Irradiated Blood
Allogeneic Bone Marrow Transplantation is Potentially Curative
Acquired or Idiopathic Aplastic Anemia (AAA) prognosis?
In Young Adults this is 90% Curative
Pure Red Cell Aplasia (PRCA)
A Very Rare Condition Where only RBC Precursors are Affected
The Etiologies & Associated Diseases are Similar to AAA
The Treatment is Immunosupression, Supportive Care & Sometimes Anti-virals
Myelodysplastic Syndromes(MDS)
Disease Characterized by Pancytopenias, Abnormally Formed RBCs, and Sometimes Immature WBCs in the Peripheral Smear
Myelodysplastic Syndromes(MDS) epidemiology and symptoms
Primarily Dz of Older Adults (Avg age presentation > 70 y.o.)
These Diseases are Not Rare
The Hx: Insidious onset of fatigue, SOB, and possibly Angina.
Splenomegaly should suggest a MPD
Myelodysplastic Syndromes(MDS) lab data
The Peripheral Smear often reveals Macrocytosis & Abnormally Formed RBCs & WBCs
The Bone Marrow is Usually Hypercellular, again with Dysplastic Changes. Blast may be Normal or Increased.
Ringed Sideroblasts Usually mean a Ringed Sideroblastic Anemia and Good Prognosis
An Increased % of Blasts is Bad
Prognosis of MDS?
5q- and Ringed Sideroblastic Anemia: ~ Average survival 5 years
RAEB-2: Average survival < 6 months
Treatment of MDS
largely supportive care
Allogeneic Bone Marrow Transplant may be appropriate for a few younger patients & is potentially curative
