Polycythemia Vera Group B Ramos, Ronald Rangel, Erika Raymundo, Nikko Rayos, Karen Recio, Maria...
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- Slide 1
- Polycythemia Vera Group B Ramos, Ronald Rangel, Erika Raymundo,
Nikko Rayos, Karen Recio, Maria Kristina Reyes, Carmen Reyes,
Jenilene Reyes, Lourdes Rivera, Laila Rivere, Djeaune Robosa,Dean
Rodas, Francis Rodriguez, Shereen Rogelio, Ma.Graciela Roque,
Marianne 1 Week 5Case 3
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- RP, 62 y.o. male CC: Left sided body weakness
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- History of Present Illness 3 wks PTA Headache with dizziness
Consulted at a health center: BP 190/110 Rx sublingual clonidine
Few hrs PTA Persistent headache Wife spotted him on the floor
unable to stand by himself Admission
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- Review of Systems Weight loss of 25% in the past 3 mos. Have
pruritus after showering Occasional claudication
- Slide 5
- Past Medical History Known Hypertensive (2yrs) Maintained on
amlodipine 5mg/tab od taken regularly Non diabetic No previous
hospitalizations
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- Personal Social History Non smoker Occasional alcoholic drinker
Family History Unremarkable
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- Physical Exam Conscious, coherent, ambulates with assistance,
not in cardiorespiratory distress BP 130/90CR 10bpmRR 21 cpmT 37.1C
Warm moist skin, plethora noted Pink palpebral conjunctivae,
anicteric sclera Symmetrical chest expansion, no retrations, clear
breath sounds Adynamic precordium, AB 5 th LICS MCL Flabby abdomen,
normoactive bowel sounds, no hepatomegaly, obliterated Traubes
space Extremities: no cyanosis, no edema, full and equal
pulses
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- Physical Exam Neuro Exam: (+) slurring of speech (+) shallow
Left nasolabial fold (+) tongue deviated to the right upon
protrusion MMT grade 2/5 on both left upper and lower extremitites
(-) Babinski
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- Laboratory Patients Results Hgb190 g/L Hct0.60 WBC18.0 x 10 9
/L Seg0.58 Lympho0.38 Mono0.02 Eos0.02 Platelet850 Normal Values
Hgb135-175 g/L Hct0.40-0.52 WBC4.0-11.0 x 10 9 /L Seg2.5-7.5
Lympho1.5-3.5 Mono0.02-0.8 Eos0.04-0.44 Platelet150-400
Interpretation: Hemoconcentration, leukocytosis with
thrombocytosis
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- Salient Features Pertinent Positives Weight loss of 25% in the
past 3 mos. Have pruritus after showering Occasional claudication
Hypertensive (BP 130/90) Plethora obliterated Traubes space
(splenomegaly) Neuro Exam:(+) slurring of speech; (+) shallow Left
nasolabial fold; (+) tongue deviated to the right upon protrusion;
MMT grade 2/5 on both left upper and lower extremitites
Hemoconcentration, leukocytosis with thrombocytosis Pertinent
Negatives Extremities: no cyanosis, no edema, full and equal pulses
no hepatomegaly
- Slide 11
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- Etiology Exact etiology is unknown Abnormalities in chromosome
such as 20q, trisomy 8, and 9p, have been documented in up to 30%
of untreated PV patients A mutation in the autoinhibitory,
pseudokinase domain of the tyrosine kinase JAK2 appears to have a
central role in the pathogenesis of PV. tyrosine kinase JAK2
replaces valine with phenylalanine (V617F), causing constitutive
activation of the kinase
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- Slide 14
- Clinical Features Splenomegaly High Hgb and Hct Uncontrolled
erythrocytosis Hypervicosity leading to neurologic symptoms:
vertigo, tinnitus, headache, visual disturbances, and TIAs.
Systolic hypertension In some patients, venous or arterial
thrombosis
- Slide 15
- Clinical Features Cerebral, cardiac, or mesenteric vessels are
commonly involved Intraabdominal venous thrombosis Digital
ischemia, easy bruising, epistaxis, acid- peptic disease, or
gastrointestinal hemorrhage Due to vascular stasis or
thrombocytosis Erythromelalgia Erythema, burning and pain in
extremities
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- Diagnosis Presents with erythrocytosis in combination with
leukocytosis, thrombocytosis or both If Px presents with with an
elevated hemoglobin or hematocrit alone, or with thrombocytosis
alone, evaluation becomes more complex because of the many
diagnostic possibilities Unless hemoglobin is >20 gm%
(hematocrit >60%), it is not possible to distinguish PV from
disorders causing plasma volume contraction Red cell mass and
plasma volume determination mandatory to establish presence of
absolute erythrocytosis Fauci et.al. Harrisons principles of
Internal Medicine 2008 17 th edition. McGraw-Hill USA
- Slide 18
- Diagnosis Once absolute erythrocytosis has been establisehd,
its cause must be determined An elevated plasma erythropoeitin
level suggests either a hypoxic cause or autonomous production
Pulmonary function Abdominal CT scan to evaluate renal and hepatic
anatomy Other labs: RBC count Mean corpuscular volume Red cell
distribution width ** bone marrow aspirate and biopsy provide no
specific diagnostic information unless there is need to establish a
myelofibrosis or exclude some other disorder Fauci et.al. Harrisons
principles of Internal Medicine 2008 17 th edition. McGraw-Hill
USA
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- True / Absolute Polycythemia Either a clonal myeloproliferative
disorder (polycythemia vera) or a nonclonal increase in red blood
cell mass that is often mediated by erythropoietin (secondary
polycythemia) Apparent / Relative Polycythemia Either a decrease in
plasma volume (relative polycythemia) or a misperception of what
constitutes the upper limit of normal values for either hemoglobin
or hematocrit Fauci, et al: Harrisons Principles of Internal
Medicine, 17 th ed. Goldman: Cecil Medicine, 23 rd ed.
- Slide 21
- APPARENT POLYCYTHEMIA A. Relative polycythemia Conditions that
cause acute depletion of plasma volume e.g. severe dehydration The
existence of chronic contraction of the plasma volume, such as
postulated for: Gaisbck's syndrome relative polycythemia associated
with hypertension and nephropathy Stress / spurious polycythemia
relative polycythemia associated with emotional stress Fauci, et
al: Harrisons Principles of Internal Medicine, 17 th ed. Goldman:
Cecil Medicine, 23 rd ed.
- Slide 22
- ABSOLUTE / TRUE POLYCYTHEMIA A. Polycythemia vera B. Secondary
polycythemia i. Congenital 1) Associated with high or normal serum
erythropoietin level 2) Associated with low serum erythropoietin
level ii. Acquired 1) Erythropoietin mediated a) Hypoxia-driven b)
Hypoxia-independent (pathologic erythropoietin production) 2) Drug
associated 3) Unknown mechanism Fauci, et al: Harrisons Principles
of Internal Medicine, 17 th ed. Goldman: Cecil Medicine, 23 rd
ed.
- Slide 23
- Secondary Polycythemia i. Congenital 1) Associated with high or
normal serum erythropoietin level 2) Associated with low serum
erythropoietin level ii. Acquired 1) Erythropoietin mediated a)
Hypoxia-driven b) Hypoxia-independent (pathologic erythropoietin
production) 2) Drug associated 3) Unknown mechanism Fauci, et al:
Harrisons Principles of Internal Medicine, 17 th ed. Goldman: Cecil
Medicine, 23 rd ed.
- Slide 24
- Secondary Polycythemia i. Congenital 1) Associated with high or
normal serum erythropoietin level 2) Associated with low serum
erythropoietin level ii. Acquired 1) Erythropoietin mediated a)
Hypoxia-driven b) Hypoxia-independent (pathologic erythropoietin
production) 2) Drug associated 3) Unknown mechanism Fauci, et al:
Harrisons Principles of Internal Medicine, 17 th ed. Goldman: Cecil
Medicine, 23 rd ed.
- Slide 25
- Secondary Polycythemia: Congenital Associated with high or
normal serum erythropoietin level Chuvash and other polycythemias
associated with von values Hippel- Lindau (VHL) gene mutation
(autosomal) recessive) High oxygen affinity hemoglobin opathy
(autosomal dominant) 2,3- Diphosphog lycerate mutase deficiency
(autosomal recessive) Pathogenetically undefined cases Associated
with low serum erythropoietin level Activating mutation of the
erythropoietin receptor (autosomal dominant) Fauci, et al:
Harrisons Principles of Internal Medicine, 17 th ed. Goldman: Cecil
Medicine, 23 rd ed.
- Slide 26
- Secondary Polycythemia i. Congenital 1) Associated with high or
normal serum erythropoietin level 2) Associated with low serum
erythropoietin level ii. Acquired 1) Erythropoietin mediated a)
Hypoxia-driven b) Hypoxia-independent (pathologic erythropoietin
production) 2) Drug associated 3) Unknown mechanism Fauci, et al:
Harrisons Principles of Internal Medicine, 17 th ed. Goldman: Cecil
Medicine, 23 rd ed.
- Slide 27
- Secondary Polycythemia: Acquired Erythropoietin mediated
Hypoxia- driven Central hypoxic process Chronic lung disease Right-
to-left cardiop ulmonar y vascular shunts High- altitude habitat
Carbon monoxide poisoning Smoker's polycythe mia (chronic carbon
monoxide exposure) Hypoven tilation syndrom es includin g sleep
apnea Peripheral hypoxic process Localize d Renal artery stenosis
Hypoxia- independent Fauci, et al: Harrisons Principles of Internal
Medicine, 17 th ed. Goldman: Cecil Medicine, 23 rd ed.
- Slide 28
- Secondary Polycythemia i. Congenital 1) Associated with high or
normal serum erythropoietin level 2) Associated with low serum
erythropoietin level ii. Acquired 1) Erythropoietin mediated a)
Hypoxia-driven b) Hypoxia-independent (pathologic erythropoietin
production) 2) Drug associated 3) Unknown mechanism Fauci, et al:
Harrisons Principles of Internal Medicine, 17 th ed. Goldman: Cecil
Medicine, 23 rd ed.
- Slide 29
- Secondary Polycythemia: Acquired Erythropoietin mediated Hypoxi
a- driven Hypoxia-independent (pathologic erythropoietin
production) Malignant tumors HCC Renal cell cancer Cerebellar
hemangio blastoma Parathyroi d carcinoma Nonmalignant conditions
Uterine leiomyo mas Renal cysts (polycys tic kidney disease)
Pheochr omocyt oma Meningi oma Fauci, et al: Harrisons Principles
of Internal Medicine, 17 th ed. Goldman: Cecil Medicine, 23 rd
ed.
- Slide 30
- Secondary Polycythemia i. Congenital ii. Acquired 1)
Erythropoietin mediated a) Hypoxia-driven b) Hypoxia-independent
(pathologic erythropoietin production) 2) Drug associated a)
Erythropoietin doping b) Treatment with androgen preparations 3)
Unknown mechanism Fauci, et al: Harrisons Principles of Internal
Medicine, 17 th ed. Goldman: Cecil Medicine, 23 rd ed.
- Slide 31
- Secondary Polycythemia i. Congenital ii. Acquired 1)
Erythropoietin mediated a) Hypoxia-driven b) Hypoxia-independent
(pathologic erythropoietin production) 2) Drug associated 3)
Unknown mechanism a) Postrenal transplant erythrocytosis Fauci, et
al: Harrisons Principles of Internal Medicine, 17 th ed. Goldman:
Cecil Medicine, 23 rd ed.
- Slide 32
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- Major clinical complications relate: directly to increase in
blood viscosity with red cell mass elevation AND indirectly to
increased turnover of red cells, leukocytes and and platelets with
the attendant increase in uric acid and cytokine production
Cytokines appears to be responsible for the increase in peptic
ulcer disease and for the pruritus associated with this disorder
Harrisons Principle of Internal Medicine 17 th ed.
- Slide 34
- Sudden massive increase in spleen size can be associated with
splenic infarction and progressive cachexia Myelofibrosis appears
to be part of the natural history of the disease but is a reactive,
reversible process that does not itself impede hematopoiesis; in
some patients, however, it is accompanied by significant
extramedullary hematopoiesis, hepatosplenomegaly, and transfusion
dependent anemia Harrisons Principle of Internal Medicine 17 th
ed.
- Slide 35
- Organomegaly can cause significant mechanical discomfort,
portal hypertension, and cachexia Erythromelalgia is a syndrome of
unknown etiology associated with thrombocytosis, primarily
involving the lower extremities and manifested usually by erythema,
warmth, and pain of the affected appendage, and occasionally
digital infarction - usually responsive to salicylates Harrisons
Principle of Internal Medicine 17 th ed.
- Slide 36
- If left uncontrolled, erythrocytosis can lead to thrombosis
involving vital organs such as the liver, heart, brain, or lungs
Patients with massive splenomegaly are particularly prone to
thrombotic events because the associated increase in plasma volume
masks the true extent of the red cell mass elevation as measured by
the hematocrit of hemoglobin level Harrisons Principle of Internal
Medicine 17 th ed.
- Slide 37
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- Phlebotomy Phlebotomy or bloodletting has been the mainstay of
therapy Remove excess cellular elements to improve the circulation
of blood by lowering the blood viscosity mainly red blood cells
Harrisons Principle of Internal Medicine 17 th ed
http://emedicine.medscape.com/article/205114-treatmentJan 23,
2009
- Slide 39
- Phlebotomy Patients with hematocrit values of less than 70% may
be bled twice a week to reduce the hematocrit to the range of less
than 45% Patients with severe plethora who have altered mentation
or associated vascular compromise can be bled more vigorously, with
daily removal of 500 mL of whole blood Harrisons Principle of
Internal Medicine 17 th ed
http://emedicine.medscape.com/article/205114-treatmentJan 23,
2009
- Slide 40
- Post-Phlebotomy volume replacement with saline solution after
each procedure to avoid postural hypotension use myelosuppressive
agents (Hydroxyurea) to avoid thrombotic or
hemorrhagiccomplications
http://emedicine.medscape.com/article/205114-treatmentJan 23,
2009
- Slide 41
- Hydroxyurea effective agent for myelosuppression Reduced the
risk of thrombosis compared with phlebotomy alone and should be the
drug of choice for patients older than 40 years however, concerns
have been raised regarding long- term risks for leukemic
transformation Harrisons Principle of Internal Medicine 17 th ed
http://emedicine.medscape.com/article/205114-treatmentJan 23,
2009
- Slide 42
- Anagrelide (Agrylin) A cyclic adenosine monophosphate
phosphodiesterase inhibitor that prevents platelet aggregation and
inhibits megakaryocyte maturation, thereby decreasing platelet
counts To date, this agent does not appear to increase the risk of
acute leukemia in patients with PV and ET over time
http://emedicine.medscape.com/article/205114-treatmentJan 23,
2009
- Slide 43
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- References Fauci, et al: Harrisons Principles of Internal
Medicine, 17 th ed. Goldman: Cecil Medicine, 23 rd ed.
- Slide 45
- A. Polycythemia vera B. Secondary polycythemia i. Congenital 1)
Associated with high or normal serum erythropoietin level a)
Chuvash and other polycythemias associated with von values
Hippel-Lindau (VHL) gene mutation (autosomal) recessive) b)
Highoxygen affinity hemoglobinopathy (autosomal dominant) c)
2,3-Diphosphoglycerate mutase deficiency (autosomal recessive) d)
Pathogenetically undefined cases 2) Associated with low serum
erythropoietin level a) Activating mutation of the erythropoietin
receptor (autosomal dominant) ii. Acquired 1) Erythropoietin
mediated a) Hypoxia-driven i. Central hypoxic process 1. Chronic
lung disease 2. Right-to-left cardiopulmonary vascular shunts 3.
High-altitude habitat 4. Carbon monoxide poisoning 5. Smoker's
polycythemia (chronic carbon monoxide exposure) 6. Hypoventilation
syndromes including sleep apnea ii. Peripheral hypoxic process 1.
Localized 2. Renal artery stenosis b) Hypoxia-independent
(pathologic erythropoietin production) i. Malignant tumors 1.
Hepatocellular carcinoma 2. Renal cell cancer 3. Cerebellar
hemangioblastoma 4. Parathyroid carcinoma ii. Nonmalignant
conditions 1. Uterine leiomyomas 2. Renal cysts (polycystic kidney
disease) 3. Pheochromocytoma 4. Meningioma 2) Drug associated a)
Erythropoietin doping b) Treatment with androgen preparations 3)
Unknown mechanism a) Postrenal transplant erythrocytosis