Download Approach to the Patient with Increased Blood Counts

Approach to the Patient with
Increased Blood Counts
Hasan Atilla Özkan, MD
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A. Approach to the patient with erythrocytosis
B. Approach to the patient with leukocytosis
C. Approach to the patient with thrombocytosis
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A. Erythrocytosis
1. General Information
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Most commonly suspected in a patient with an
abnormally high result an one or more of the
following blood tests
- Htc: >48% woman, >52% man
- Hgb: > 16.5 woman, > 18.5 man
- RBC count
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2. Terminology
• Relative polycythemia: due to reduced plasma
volume
• Absolute polycythemia: increased red cell mass
- primary polycythemia; caused by aquired or
inherited mutation leading to an abnormality
within RBC progenitors
- secondary polycythemia; caused by a
circulating factors stimulating erythropoiesis,
usually erythropoietin (hypoxia, Eposecreting tumors)
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• Combined polycythemia; increased RCM +
reduced plasma volume (smokers polycythemia)
• Inapparent polycythemia; both RCM +
plasma volume increased. Need for blood
volume studies
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3. Physiology of erythropoiesis
• RBC are derived from the pluripotent
hematopoietic stem cell
• Under normal conditions, the earliest, erythroidcommited progenitor cells depend on the Epo to
further differentiate and produce RBC
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• 90% of the circulating Epo is synthesized by the
kidneys in response to hypoxic signal
- anemia
- reduced Hgb-O2 saturation (hypoxemia)
- decreased O2 released from Hgb (high-O2affinity hemoglobinopathies)
- reduced O2 delivery to kidney (vascular
occulusion)
• A negative feedback inhibition mechanism down
regulates Epo production with increasing O2
delivery
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4. Evaluation
Do not forget: Most common cause of
polycythemia is hypoxia secondary to
pulmonary disease
a) History:
• Symtoms pertaining to altered lung function
• Living at high attitude
• İntracardiac or intrapulmonary shunts
• Renal tx
• Hemorragic or thrombotic events
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• Post-bath pruritus
• Family history
• Medications
• Smoking history
• Chronic exposure to carbon monoxide
• Pulmonary arteriovenous malformations
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b) Physical examination
• Cyanosis in the lips, earlobes and fingers
• Clubbing in the nailbeds
• Shortness of the breath
• Plethoric face, painful erythema
• Cardiac murmurs
• Hepato-splenomegaly
• purple striae, hirsutism, buffalo hump, central
obesity (Chushing syndrome)
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c) Laboratory testing
• Hgb, Htc and RBC count
• A high RBC count with reduced Hgb and MCV –
thalassemia minor
• Elevated WBC and/or plt count and/or reduced
MCV – PV
• Testing for Jak-2 mutation
• Hematuria with a high Epo – renal cell Ca
• Abnormal liver function – hepatoma
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• Blood volume measurements
- RBC mass: 24 to 30 ml/kg
- plasma volume: 39-49 ml/kg
• Pulse oximetry, arterial oxygen tension
• Serum erythropoietin
- low Epo with erythrocytosis – PV
- normal-high Epo – secondary eythrocytosis
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• Tumors may lead to eythrocytosis
- hepatocellular Ca
- renal cell Ca
- hemangioblastoma
- pheochromocytoma
- uterine myoma
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d) Management of secondary erythrocytosis
• Control of the underlying disease
• Limited phlebotomy
- < 45% - man
- < 42% - woman
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B. Leukocytosis
• Normal total WBC count; 4000-11000 cells/µL
• Leukocytosis WBC > 11000
• Leukomoid rxn -WBC >50000 (other than leukemia)
• Aproximattely 60% mature neutrophils
• Leukocytosis is most commonly due to an
increase in the absolute number of mature
neutrophils (neutrophilia)
• But, also reflect increase in lymphocytes,
eosinophils, monocytes, basophils or blast cells,
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• Normal leukocyte count, differential count:
WBC
4400-11000
Segmented N
1800-7000
Band
0-700
Eosinophils
0-450
Basophils
0-200
Lymphocytes
1000-4800
Monocytes
0-800
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• ANC= WBC X percent (PMNs + bands) / 100
• Neutrophilic leukocytosis:
- WBC > 11000 + ANC > 7000
• Neutrophilia:
- WBC < 11000 + ANC > 7000
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• Evaluation of a patient with leukocytosis should
include a CBC, Plt count, WBC differential and
examination of the peripheral blood smear;
- presence of a ‘left shift’
- evaluation for infection/inflammation
- presence of anemia or polycythemia,
thrombocytemia or thrombocytosis, and/or abnormal
cells
- presence of predominance of lymphocytes
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Neutrophilia
• Mechanism;
- increased production in bone marrow
- increased released from stores
- shift from marginal poll to circulation
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1) Evaluation of neutrophilia
a)
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History;
İnflammation or infection
Smoking
Pregnancy
Emotional stress
Prior hematologic disease
Heavy exercise
Trauma, surgery, thermal burn, electric shock
Splenectomy
medications
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b) Physical examination; to determine presence
or absence of infection, inflammation or
malignancy
• Fever
• Hypotention, shock, tacycardia, hypothermia
• Evidence of infection
• Abdominal rebound, tenderness
• Joint swelling, erythema
• Hepatosplenomegaly
• Lymphadenopathy
• Diarrhea
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c) Laboratory testing
• WBC differantial and peripheral blood smear
- left shift, toxic granulation, döhle body – infection
- howell-joly bodies – splenectomy or asplenia
- blasts – leukemia
- peripheral blood smear mimicing bone marrow – CML
- leukocytosis + thrombocytosis ± erythrocytosis – MPD
- leukoerytroblastic picture – infiltrative marrow disease
- platelet clumping, cryoglobulinemia
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• Bone marrow examination: When ?
- in the presence of leukomoid rxn,
leukoerythroblastic picture or immature cells
on the peripheral smear
• CRP, ESR
• Cultures, imaging, etc
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Monocytosis
• > 10% of total WBC or > 800/µL
• Causes;
- infections (brucellosis, varicella-zoster, bacterial
endocarditis, tbc, malaria, thyhoid fever, syphilis)
- inflammatory (eg. Sarcoidosis, inflammatory bowel
disease)
- treatment with steroids, GM-CSF
- pregnancy
- malignancy ;
- chronic myelomonocytic leukemia
- acute monoblastic/myelomonocytic leukemia
- hodgkin lymphoma
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Lymphocytosis
• Subset of WBC that form an integral part of the
immune system
• Facilitate humoral and cellular immunity againts
foreign proteins and pathogens
• Absolue lymphocyte count (ALC) = WBC X
percent lymphocytes/100
• Lymphocytosis: ALC > 4000/µL
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• Lymphocyte subpopulation
- T cells (eg. CD3+) – 60-80%
* T helper (CD4+) – 60-70 %
* T suppressor (CD8+) – 30-40 %
- B cells (eg. CD20+) – 10-20%
- NK cells (eg. CD56+) – 5-10 %
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• Lymphocytosis;
- Reactive lymphocytosis - polyclonal nonmalignant
- Clonal lymphocytosis – almost always
lymphoproliferative disorder
• Blood lymphocyte morphology is very important
for diagnosis
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• Causes of malignant and premalignant
lymphocytosis:
- thymoma
- hereditary polyclonal B cell lymphocytosis
- monoclonal B cell lymphocytosis
- chronic lymphocytic leukemia
- lymphoproliferative disease of large granular
lymphocytes
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Eosinophilia
• > 500/µL
- 500-1000 : mild
- 1000-5000: modarate
- > 5000 : severe
• Catagories of eosinophilia;
- primary: usually due to hematologic malignancy
- secondary: allergic disorders, parasitic infections,
medications, etc..
- idiopathic
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Basophilia
• > 200/µL
• Most common causes;
- myeloproliferative disorders (CML, PV, PMF, ET)
- hematologic malignancy (basophilic leukemia,
mastocytosis, hypereosinophilic syndrome, atypical
acute or chronic leukemias, MDS)
- allergic or inflammatory reactions (hypersensitivity rxn,
ulserative colitis, RA)
- endocrinopathy (hypothroidism, administration of
estrogens)
- infections (viral, Tbc, helminth infections)
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C. Thrombocytosis
• > 450.000/µL
• Two questions should be addressed in any
patient with newly diagnosed thrombocytosis:
- a reactive phenomenon or a clonal hematologic
disorder
- what is the risk to the patient and how should it be
managed ?
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a) Definitions
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Reactive thrombocytosis (eg. Surgery, trauma,
infection)
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Autonomous (primary) thrombocytosis
(eg. PV, CML, PMF, 5q-syndrome)
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1) Reactive Thrombocytosis
• RT is more common than AT
• Coomon causes of extreme RT (>106) are;
- infection – 31%
- postsplenectomy – 19%
- malignancy – 14%
- trauma – 14%
- inflammation – 9%
- blood loss – 6%
- rebound thrombocytosis – 3%
- unknown – 4%
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• Thrombopoietic growth factors (thrombopoietin,
IL-6) have been implicated as the cause of RT in
various infections, inflammatory, malignant,
necrotic, and traumatic processes
• Symptoms;
- vasomotor (headache, visiual symptoms, chest pain,
acral dysesthesia, erythromelalgia)
- thrombosis
- bleeding
• Degree of thrombocytosis does not predict the
likelihood of AT. But, thrombohemorrahagic
manifestations suggest the diagnosis of AT
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Erythromelalgia
Plethoric face
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2) Spurious (False) Thrombocytosis
• mixed cryoglobulinemia
• Cytoplasmic fragments (severe hemolysis, burn, etc)
3) Autonomous (primary) Thrombocytosis
• Essential thrombocythemia
• CML
• PV
• MDS (5q-syndrome)
• Acute myeloid leukemia (t(3;3) and inv(3) in AML)
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b) Management
1) Bleeding:
- discontinue the use of any antiaggregant agent
- laboratory evaluation for DIC and coagulation factor
deficiency
- platelet and/or FFP transfusion
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2) Thrombosis
• Occlusion of the hepatic and/or inferior vena cava, portal
or splenic vein suggests AT (especially in female < 45 y)
• Platelet apheresis, if Plt > 800.000
• Platelet lowering agent to Plt < 400.000 (hydroxyurea,
anegralide)
• Testing for other thrombotic causes
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3) Vasomotor symptoms
• Low dose aspirin
• Calcium – chanel blockers
• penthoxyphilline
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