Polisitemia Vera

Essentials of Diagnosis
• Increased red blood cell mass.
• Splenomegaly.
• Normal arterial oxygen saturation.
• Usually elevated white blood count and
platelet count.
 DD Polisitemia Vera
• Polisitemia spuria : ↓ cairan tubuh 
pemakaian diuretik, sebab lain
• Polisitemia sekunder :
– Hipoksia : penyakit jantung, paru, ketinggian
– HbCO2 : merokok
– Lesi ginjal
– Tumor dgn sekresi EPO
– Hb abnormal
 Causes of polycythemia.
 Spurious polycythemia
 Primary polycythemia : PV
 Secondary polycythemia
1. Hypoxia: cardiac disease, pulmonary
disease, high altitude
2. Carboxyhemoglobin: smoking
3. Renal lesions
4. Erythropoietin-secreting tumors (rare)
 Sign and simptom
• Symptoms related to expanded blood volume and increased
blood viscosity.
• Common complaints: headache, dizziness, tinnitus, blurred
vision, and fatigue. Generalized pruritus,and epistaxis.
• 60% are men, and the median age at presentation is 60 years.
Polycythemia rarely occurs in persons under age 40 years.
• Physical examination: reveals plethora and engorged retinal
veins. Spleenomegaly in 75% of cases but is nearly always
enlarged when imaged
• Thrombosis is the most common complication of
polycythemia vera and the major cause of morbidity and
death.
• There is a high incidence of peptic ulcer disease.
 Laboratory Finding
• Hematocrit above normal, at times greater than 60%.
• Red blood cell morphology is normal.
• The red blood cell mass is elevated.
• The white blood count is elevated to 10,000-20,000/uL
• The platelet count is variably increased, sometimes to counts exceeding
1,000,000/uL.
• Platelet morphology is usually normal.
• The bone marrow is hypercellular, with panhyperplasia
• Iron stores are usually absent from the bone marrow
• Overproduction of uric acid may lead to hyperuricemia.
• Microcytosis, hypochromia, and poikilocytosis may result from iron
deficiency
• Progressive hypersplenism may also lead to elliptocytosis.
 Differensial Diagnosis
Laboratory features of myeloproliferative disorders.

WhiteCount Hematocrit Platelet Count Red cellMorphology

• Chronic myeloid leukemia I N N or I N
• Myelofibrosis N or D or I N or I D or N or I Abn
• Polycythemia vera N or I I N or I N
• Essential thrombocytosis N or I N I N
 Treatment
• Phlebotomy. One unit of blood (approximately 500
mL) weekly target: less than 45%.
• Myelosuppressive therapy : a high phlebotomy
requirement, thrombocytosis, and intractable
pruritus. Hydroxyurea >> Alkylating because of less
leukemogenic potential. The usual dose is 500-1500
mg/d orally Target: platelets < 500,000/uL and
neutrophil count < 2000/uL. Anagrelide is a new drug
for trombositosis
• Low-dose aspirin (81-325 mg daily) has been shown
to reduce the risk of thrombosis.
 Prognosis
• Polycythemia is an indolent disease with median
survival of 11-15 years.
• The major cause of morbidity and mortality is arterial
thrombosis.
• Polycythemia vera may convert to myelofibrosis or to
chronic myelogenous leukemia. In approximately 5%
of cases, the disorder progresses to acute
myelogenous leukemia, which is usually refractory to
therapy.
 Trombositosis Esensial
• Peningkatan trombosit tanpa sebab lain
• Massa eritrosit N
• Kromosom Philadelphia (-)  DD dgn CML
• Klinis berisiko trombosis, atau justru terjadi
perdarahan krn defek platelet kualitatif
• DD :
* Polisitemia Vera
* Trombositosis reaktif (pada infeksi, anemia def besi,
perdarahan) 
– Jumlah trombosit pd trombositosis reaktif jarang > 1
juta/mmk
 Essential Trombositosis
Essentials of Diagnosis
• Elevated platelet count in absence of other
causes.
• Normal red blood cell mass.
• Absence of Philadelphia chromosome.
 Symptoms and Signs
• Median age: 50-60 years, slightly increased incidence
in women.
• Finding of an elevated platelet count.
• First sign is thrombosis. Venous thromboses may
occur in unusual sites such as the mesenteric,
hepatic, or portal vein.
• Some patients experience erythromelalgia(painful
burning and erythema)
• Bleeding
• Splenomegaly is present in at least 25% of patients.
 Laboratory Findings
• Elevated platelet count is the hallmark of this disorder, and
may be over 2,000,000/uL.
• WBC mildly elevated (not above 30,000/uL), but with some
immature myeloid forms.
• The hematocrit is normal.
• The peripheral blood smear reveals large platelets, but giant
degranulated forms seen in myelofibrosis are not observed.
• Red blood cell morphology is normal.
• The bleeding time is prolonged in 20% of patients.
• The bone marrow : increased megakaryocytes but no other
morphologic abnormalities.
• The Philadelphia chromosome is absent to differentiate from
chronic myeloid leukemia.
 Differensial Diagnosis
Laboratory features of myeloproliferative disorders.

WhiteCount Hematocrit Platelet Count Red cellMorphology

• Chronic myeloid leukemia I N N or I N
• Myelofibrosis N or D or I N or I D or N or I Abn
• Polycythemia vera N or I I N or I N
• Essential thrombocytosis N or I N I N
 Treatment
• Standard therapy has consisted of hydroxyurea in a
dose of 0.5-2 g/d.
• Anagrelide is highly effective in a dose of 2-4 mg/d
but may cause headache, mild anemia, and
peripheral edema, and in high doses congestive
heart failure.
• Vasomotor symptoms such as erythromelalgia and
paresthesias respond rapidly to aspirin and
eventually to control of the platelet count.
• Plateletpheresis.
 Prognosis
• Essential thrombocytosis is an indolent disorder
• Average survival is longer than 15 years from
diagnosis
• The major source of morbidity — thrombosis — can
be reduced by appropriate platelet control.
• The bone marrow may become fibrotic, and massive
splenomegaly may occur, sometimes with splenic
infarction.
• There is a 10-15% risk of progression to myelofibrosis
after 15 years, and a 1-5% risk of transformation to
acute leukemia over 20 year
 IDIOPATHIC (AUTOIMMUNE)
THROMBOCYTOPENIC PURPURA
Essentials of Diagnosis
• Isolated thrombocytopenia.
• Other hematopoietic cell lines normal.
• No systemic illness.
• Spleen not palpable.
• Normal bone marrow with normal or
increased megakaryocytes.
 Patophysiology
• ITP: autoimmune disorder in which an IgG
autoantibody is formed that binds to platelets.
• Platelets are not destroyed by direct lysis.
• Destruction takes place in the spleen, where
splenic macrophages with Fc receptors bind to
antibody-coated platelets.
• Splenectomy is highly effective therapy.
 Symptoms and Signs
• ITP commonly in childhood
• Precipitated by viral infection and usually self-
limited.
• Adult form is usually a chronic disease and only
infrequently follows a viral infection.
• Incidence between ages 20 and 50 years, and there is
a 2:1 female predominance.
• Presenting complaint is mucosal or skin bleeding
(epistaxis, oral bleeding, menorrhagia, purpura, and
petechiae).
• An enlarged spleen should lead one to doubt the
diagnosis.
 Laboratory Findings
• The hallmark of the disease is thrombocytopenia,
with platelet counts that may be less than 10,000/uL.
• Other counts are usually normal except for
occasional mild anemia, which can be explained by
bleeding or associated hemolysis (Evans's syndrome).
• Peripheral blood cell morphology is normal except
that platelets are slightly enlarged
(megathrombocytes).
• The bone marrow will appear normal, with a normal
or increased number of megakaryocytes.
• Coagulation studies will be entirely normal.
 Differensial Diagnosis
Causes of thrombocytopenia.
• Bone marrow disorders
1. Aplastic anemia
2. Hematologic malignancies
3. Myelodysplasia
4. Megaloblastic anemia
5. Chronic alcoholism
• Nonmarrow disorders
1. Immune disorders
2. Idiopathic thrombocytopenic purpura
3. Drug-induced
4. Secondary (CLL, SLE)1
 Treatment
• Initial treatment is with prednisone, 1-2 mg/kg/d.
Prednisone works primarily by decreasing the affinity
of splenic macrophages, reduces the binding of
antibody to the platelet surface, decrease antibody
production, enhanced vascular stability.
• the risk of bleeding is small with platelet counts
above 50,000/uL.
• An alternative steroid regimen is the use of high-
dose dexamethasone, 40 mg/d for 4 days.
• Splenectomy is the most definitive treatment for
idiopathic thrombocytopenic purpura, Splenectomy
is indicated if patients do not respond to prednisone.
Splenectomy can be performed safely even with
platelet counts less than 10,000/uL. CR 80%
 Treatment
• High-dose intravenous immunoglobulin, 1 g/kg for 1
or 2 days, is highly effective in rapidly raising the
platelet count. Use for bleeding or emergencies
situations.
• Danazol, vincristine, azathioprine, cyclosporine, and
cyclophosphamide.
• Rituximab can produce good responses in some
patients with refractory disease.
• Platelet transfusions are rarely used in the treatment
of idiopathic thrombocytopenic purpura,
 Prognosis
• The prognosis for remission is good.
• The major concern during the initial phases is
cerebral hemorrhage, which becomes a risk
when the platelet count is less than 5000/uL.
• Very low platelet counts caused fatal bleeding
is rare.
THROMBOTIC THROMBOCYTOPENIC PURPURA

Essentials of Diagnosis
• Thrombocytopenia.
• Microangiopathic hemolytic anemia.
• Neurologic and renal abnormalities, fever.
• Reduced level of ADAMTS13.
• Normal coagulation tests.
• Elevated serum LDH.
 Introducing
• TTP is an uncommon syndrome with
microangiopathic hemolytic anemia,
thrombocytopenia, and a markedly elevated serum
LDH.
• Deficiency of a von Willebrand factor-cleaving
protease, ADAMTS13, to platelet agglutination and
adhesion to endothelium.
• TTP is seen primarily in young adults between ages
20 and 50 years, female predominance.
• The syndrome is occasionally precipitated by
estrogen use, pregnancy, drugs, or infections. The
most common drugs implicated are quinine and
ticlopidine.
 Symptoms and Signs

• Anemia, bleeding, or neurologic abnormalities.

• Neurologic symptoms include headache,
confusion, aphasia, and alterations in
consciousness from lethargy to coma. With more
advanced disease, hemiparesis and seizures may
occur.
• On examination, the patient appears acutely ill
and is usually febrile. Pallor, purpura, petechiae,
• Patients may have abdominal pain and
tenderness due to pancreatitis.
 Differential Diagnosis

• The normal values of coagulation tests

differentiate TTP from DIC.
• Other conditions causing microangiopathic
should be excluded
• Evans's syndrome is the combination of
autoimmune thrombocytopenia and
autoimmune hemolytic
 Laboratory Findings
• Anemia
• Reticulocytosis and circulating nucleated red
blood cells.
• The hallmark is a microangiopathic blood
picture with fragmented red blood cells
• Thrombocytopenia is invariably present and
may be severe.
• Increasing indirect bilirubin
• LDH is markedly elevated in proportion to the
severity of hemolysis;
• Coombs test is negative.
• Coagulation tests (prothrombin time, partial
thromboplastin time, fibrinogen) are normal
unless ischemic tissue damage causes
secondary disseminated intravascular
coagulation
• (DIC) present elevated fibrin degradation
products may be seen.
• ADAMTS13 is usually absent during active
disease.
• Pathologically, there may be thrombi in
capillaries and small arteries, with no
evidence of inflammation.
 Differensial Diagnosis
• Evans's syndrome is the combination of autoimmune
thrombocytopenia and autoimmune hemolytic
anemia, but the peripheral smear will show
spherocytes and not red blood cell fragments.
• TTP and hemolytic-uremic syndrome are not distinct
disease entities, TTP characterized by more
neurologic and severe thrombocytopenia and
hemolytic-uremic syndrome with more renal failure.
 Treatment
• Plasmapheresis. 60 to 80 mL/kg of plasma should be removed
and replaced with fresh-frozen plasma.
• Treatment should be continued daily until the patient is in
complete remission.
• Prednisone and antiplatelet agents (aspirin [325 mg three
times daily] and dipyridamole [75 mg three times daily])
• The combination of splenectomy, corticosteroids, and dextran
has been used with success.
• Splenectomy performed in remission may prevent subsequent
relapses.
• Immunosuppression with drugs such as cyclophosphamide
has also been effective.
 Prognosis
• With plasmapheresis, 80 to 90 percent of
patients now recover completely.
• Neurologic abnormalities are almost always
completely reversed.
• Most complete responses are durable, but in
20% of cases the disease will be chronic and
relapsing.
Transfusi Darah
 Transfusi Darah
• Transfusi Darah Lengkap
• Transfusi Sel Darah Merah
• Uji Kompatibilitas
• Komplikasi Transfusi
• Transfusi Platelet
• Transfusi Plasma
 Transfusi Darah Lengkap
= (Fresh) Whole Blood/FWB
• Indikasi FWB/WB : kehilangan darah akut yg cukup
mengakibatkan hipovelemia
• FWB/WB akan mengganti Hb dan mengakibatkan
ekspansi volume
• Transfusi komponen darah (PRC, FFP, dll) lebih
diutamakan bila tidak terdapat indikasi tersebut di
atas, ok. risiko overload volume dan reaksi transfusi
 Transfusi Sel Darah Merah
• Umum digunakan PRC (packed red cell). WRC
(washed red cell) dipergunakan untuk memperkecil
risiko reaksi alergi
• Indikasi mulai transfusi
– pasien Hb 7 – 9 dgn gejala, atau kelainan kardiovaskuler
– pasien Hb < 7 dgn/tanpa gejala
• Satu unit PRC menaikkan Hb sekitar 1 g/dl
• Evaluasi Hb dilakukan 6 jam pasca transfusi
 Uji Kompabilitas
• Rutin diujikan : sistem ABO dan Rh
• Usahakan : gol darah ABO dan Rh antara donor dan
resipien sama, dgn cross-matched mayor dan minor
negatif
• Dalam keadaan emergensi, tipe O- adalah donor
universal, tipe AB+ adalah resipien universal
• Umumnya, Rh- aman bila diberikan pd Rh+
Komplikasi Transfusi = Reaksi Transfusi
• Reaksi transfusi hemolitik
– Akibat inkompabilitas ABO  hemolisis intravaskuler
– Demam/menggigil, nyeri kepala/punggung  syok, DIC, ARF
• Reaksi leukoaglutinin
– Rx thd antigen lekosit pd transfusi berulang/kehamilan
– Demam/menggigil 12 jam stlh transfusi, tanpa hemolisis
• Reaksi anafilaktik
– Akibat adanya antibodi thd IgA donor  bronkospasme, urtika
• Transmisi penyakit
– Hepatitis B  1 : 200.000 unit
– HIV  1 : 250.00 unit
– Hepatitis C  1 : 3300 unit
 Transfusi Trombosit
• Ideal : apheresis/plateletpharesis = prosedur
pengambilan komponen darah dari donor tunggal,
untuk menghindari alloimunisasi. Problem :
keterbatasan mesin apheresis
• 1 unit TC (thrombocyte concentrate) diharapkan
menaikkan 10.000 sel/mmk. Adanya antibodi thd
platelet dapat mengakibatkan kenaikan AT tdk
optimal
• Evaluasi AT dilakukan 1 dan 24 jam pasca transfusi
 Transfusi Plasma
• Fresh frozen plasma (FFP) merupakan sumber faktor
koagulasi, fibrinogen, antitrombin, protein C dan S.
• FFP diindikasikan untuk mengkoreksi kondisi
defisiensi faktor koagulan, misal
– Hemofilia A, B, von Willebrand disease
– Sirosis hati
– DIC
 Kepustakaan
• Dzieckowski, J.S., Anderson, K.C., 2005,
Transfusion and Pheresis Therapy, in D.L.
Kasper et al, Harrison’s Manual of Medicine,
17th Ed, McGraw Hil, New York
• Linker, C.A., 2007. Blood, in S.J. McPhee et al.,
CMDT, 46th Ed, McGraw Hill, New York
Alhamdulillahi Robbil Alamien