Outline Anemia Thrombocytopenia Neutropenia Coagulation disorders Lymphoma Terese Winslow Lydia Kibiuk http stemcellsnihgov info scireport pageschapter5aspx Terese Winslow Lydia ID: 779651
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Slide1
Hematology & HIV
Katherine Marx, MS, MPH, FNP-BC
Slide2Outline
Anemia
Thrombocytopenia
Neutropenia
Coagulation disorders
Lymphoma
Slide3Terese
Winslow, Lydia
Kibiuk
, http://
stemcells.nih.gov
/info/
scireport
/pages/chapter5.aspx
Slide4Terese
Winslow, Lydia
Kibiuk
, http://
stemcells.nih.gov
/info/
scireport
/pages/chapter5.aspx
Red
Blood
Cells
Slide5WHO Criteria:
Anemia if hemoglobin g/dl is below:
Nutritional
Anaemias
. Report of a WHO Scientific Group. WHO Tech Rep Ser. 1968;405:1-40
Slide6Blood. 2006 Mar 1; 107(5): 1747–1750
.
Slide7Anemia is common
Percent of HIV-infected adults with anemia
Sullivan PS, et al. Blood. 1998; 91 (1) 301.
Slide8Anemia
associated with increased risk of death
CD4
Status
Risk Ratio
CD4 <200
1.56
CD4
>200
2.48
Sullivan PS, et al. Blood. 1998; 91 (1) 301
.
Slide9Causes of anemia
HIV
Drugs
Infections
Malignancy
Deficiencies
Production
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide10Causes of anemia
Hemolysis
Drugs
Infection
GI bleed
Hypersplenism
Loss
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide11Anemia: identifying the causes
History:
Medications
Diet
Bleeding
Functional assessment
Symptoms of infection and B symptoms: including fatigue, fever, night sweats, cough, weight loss
Volberding
PA. Clin Ther
. 2000 Sep:22(9): 1004-1020
.
Slide12Anemia: identifying the causes
Medication list:
Zidovudine
Ganciclovir
Ribaviron
TMP-SMX
Dapsone
Amphotericin BCeftriaxoneSubstance use:EcstasyAlcohol
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide13Anemia: identifying the causes
Labwork
:
CBC, red cell indices, reticulocytes, blood smear
Serum bilirubin, LDH,
haptoglobin
, direct Coombs
G6PD levelB12, folate
, iron studiesTests for infections MAI, MTB, histoplasma, CMV, EBV, Parvovirus B19, hepatitis, CMVRefractory cases: EPO level, bone marrow biopsy
Volberding
PA.
Clin
Ther
. 2000 Sep:22(9): 1004-1020
.
Slide14Anemia: identifying the causes
Physical exam
Vital signs
Oral
Skin
Opthalmological
Cardiac
Abdominal/ GastrointestinalNeurologicalFunctional
Volberding PA. Clin
Ther
. 2000 Sep:22(9): 1004-1020
.
Slide15http://
library.med.utah.edu
/
Slide16http://
library.med.utah.edu
/
Redig
AJ, Berliner N. Hematology Am
Soc
Hematol Educ Program. 2013: 377-81.
RBC 4.28 L
HGB 9.7 L
HCT 29.9 L
MCV 80.8
MCH 26.2
MCHC 37,0
RDW 14.5
Ferritin 55
Reticulocyte 0.3 L
Count
Ferritin 4 L
Reticulocyte 0.3 L
Count
Iron deficiency
Anemia of chronic disease or
inflammantion
Slide17http://
library.med.utah.edu
/
Slide18Treatment of anemia
Remove the cause
Drugs
Treat the cause
HIV (give
antiretrovirals
)
InfectionsMalignancyTreat the symptoms
EPOTransfusionVolberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Volberding
PA.
Clin
Ther. 2000 Sep:22(9): 1004-1020.
Slide19Case: anemia
45
yo
AA
female
with
AIDSAnemia (Hb
8, microcytic, hypochromic)VL >100K
CD4
67
Slide20Case: neutropenia
Antiretrovirals
+
Replace TMX-
SMP
+
Supplement iron
VL undetectable
CD4 improved
Hb
did not improve
Low EPO
Start
erythropoieten
Hb
improved
Acute renal failure
Hemodialysis
Slide21Terese
Winslow, Lydia
Kibiuk
, http://
stemcells.nih.gov
/info/
scireport
/pages/chapter5.aspx
Platelets
Slide22Thrombocytopenia
<150,000
μL
thrombocytopenia
<100,000
μL bleeding time prolonged<30,000 μL usually treated
<10,000 μL spontaneous bleeding risk Rodeghiero
F, et al. Blood. 2009; 113(11).
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Wandt
H, et al. Blood. 1998;91-3601.
Slide23Indicator condition
:
Thrombocytopenia
Test for HIV infection
Sullivan AK, et al.
PLoS
One. 2013;8:e52845.
Søgaard
OS et al.
PloS
One. 2012;7:e32538.
Slide24Causes of thrombocytopenia
Drugs
Infections
Malignancy
Deficiencies
Production
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide25Causes of thrombocytopenia
Immune thrombocytopenic
purpura
Thrombotic thrombocytopenic
purpura
Hypersplenism
Drugs
Loss
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide26Thrombocytopenia:
identifying the causes
History:
Bleeding
Symptoms of infection or B symptoms
Diet
Slide27Thrombocytopenia:
identifying the causes
Medication list:
TMP-SMX
Pentamidine
Pyrimethamine
Ganciclovir
Fluconazole
Alpha-interferonRifabutonClarithromycinDidanosineAmphotericin B
Indinavir
Ritonavir
Saquinavir
Interferon
Heparin
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide28Thrombocytopenia:
identifying the causes
Labwork
:
CBC
Tests for infections
MAI, MTB,
histoplasma, CMV, EBV, Parvovirus B19, hepatitis, Bartonella
Slide29Thrombocytopenia:
identifying the causes
Physical exam
Vital signs
Skin
Abdominal
Mucosal sites for bleeding: Oral, GYN, anal
Volberding
PA. Clin Ther. 2000 Sep:22(9): 1004-1020.
Slide30Treatment of thrombocytopenia
Remove the cause
Drugs
Treat the cause
HIV (give
antiretrovirals
)
InfectionsMalignancyPrevent bleeding
ITP: Glucocorticoids, IVIG, IV anti-D therapy, splenectomy, danazol, interferon, vincristine
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide31Terese
Winslow, Lydia
Kibiuk
, http://
stemcells.nih.gov
/info/
scireport
/pages/chapter5.aspx
Neutrophils
Slide32Neutropenia
Absolute neutrophil count (ANC):
< 1500/
μL
neutropenia
<1000/
μL
increased risk of infection< 500/μL severely increased risk of infection
Moore RD, et al. Arch Intern Med 1995; 155:1965.Keiser P, et al. Am J Med Sci. 1996; 312:118.Jacobson MA, et al. Arch Intern Med. 1997; 157:1825.
Slide33Causes of neutropenia
Drugs
Infections
Malignancy
Deficiencies
Production
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide34Causes of neutropenia
Autoimmune neutropenia
Hypersplenism
Loss
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide35Neutropenia:
identifying the causes
Medications:
Ganciclovir
Zidovudine
TMP-SMX
Rifabutin
Chemotherapy
DapsoneAmphotericin BRitonavirNelvinavir
History:
Fever
Other symptoms of infection
B-symptoms
Diet
Volberding
PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Slide36Neutropenia:
identifying the causes
Labwork
:
CBC with differential
Tests for infections
MAI, MTB,
histoplasma, CMV, EBV, Parvovirus B19
Slide37Neutropenia:
identifying the causes
Physical exam:
Vital signs
Skin
Abdomen
Oral
Slide38Treatment of neutropenia
Remove the cause
Drugs
Treat the cause
HIV (give
antiretrovirals
)
InfectionsMalignancyIncrease the neutrophils Colony stimulating factors (G-CSF, GM-CSF)
Volberding PA, Baker KR, Levine AM, Hematology Am
Soc
Hematol
Educ
Program. 2003:
294-313.
Kuritzkes
DR et al. AIDS 1998; 12:65.
Slide39Case: neutropenia
56
yo
AA male with AIDS, avascular necrosis
A
nemia (
Hb
10, normocytic, normochromic)Neutropenia (ANC 600)Thrombocytopenia (platelets 45K)VL 50K
CD4 35
Slide40Case: neutropenia
Antiretrovirals
+
Replace TMX-SMP
VL undetectable
CD4 declined
ANC declined
Platelets declined
Bone marrow biopsy:
myelodysplastic
syndrome
Granulocyte colony stimulating factor
Slide41Coagulation disorders:
Venous thromboembolism
R
isk factors
Age
Smoking
Immobility
Family historyhospitalization
Crum-Cianflone, Weekes J, Bavaro
M. AIDS Patient Care STDS. 2008;(10):771-778.
.
Slide42Coagulation disorders
Venous thromboembolism
R
isk factors
Age
Smoking
Immobility
Family historyHospitalization
MalignancyCrum-Cianflone, Weekes J,
Bavaro
M. AIDS Patient Care STDS. 2008;(10):771-778.
Jacobson MC et al. CID. 2004;39:1214.
.
HIV-Related
Coagulopathy
HIV
OI
Medications
Low CD4, high VL
Slide43Slide44Slide45Case: coagulation disorder
29
yo
AA male
AIDS and
cryptococcal
meningitis
CD4 6VL undetectable for 3 monthsSwollen, painful left thigh
Slide46Case: coagulation disorder
Anticoagulation
Inferior vena cava filter
Antiretrovirals
Antiphospholipid
ab
INR: difficult to manage
Stroke
Recurrent VTE
Slide47Terese
Winslow, Lydia
Kibiuk
, http://
stemcells.nih.gov
/info/
scireport
/pages/chapter5.aspx
B Lymphocytes
Slide48Lymph Node
http://
www.dartmouth.edu
/~
nlevy
/pln3.html
Slide49HIV-related Non-Hodgkin Lymphoma
Systemic NHL
Primary CNS Lymphoma
Primary Effusion Lymphoma
DLBCL
Burkitt
-like
Slide50HIV-related Non-Hodgkin Lymphoma
Types
Systemic NHL
Primary CNS Lymphoma
Primary Effusion Lymphoma
DLBCL
Burkitt
-like
70-90%
10-15%
<1%
Knowles DM.
Hematol
Oncol
Clin
North Am 2003;17:785
.
Slide51HIV-related Non-Hodgkin Lymphoma
Survival
Systemic NHL
Primary CNS Lymphoma
Primary Effusion Lymphoma
DLBCL
Burkitt
-like
56/ 44
24/23
53/44
53/50
Gopal
S et al. J
Natl
Cancer Inst. 2013;105(16):1221.
Slide52Risk factors for HIV-associated NHL
Immunosuppression
Increased viral load
Viral co-infection: EBV, HHV8
CD4 50 100 200
Primary CNS
Lymphoma
DLBCL
Burkitt
Biggar
RJ et al. J
Natl
Cancer Inst. 2007;99(12):962
Guech-Ongey
M, et al.
Bood
. 2010;116(25):5600..
Hamilton-
Dutoit
SJ et al. Lancet 1989:1:554.
Cesarman
E, et al. N
Engl
J Med. 1995;332(18):1186.
Slide53Presentation: systemic HIV-related NHL
First symptoms:
B Symptoms
Fever
Night sweats
Weight loss
Generalized
lymphadenopathyFever of unknown origin
Gabarre J, et al. Am J Med. 2001;111(9):704.
Bissuel
F, et al. J Intern Med. 1994;236(5);529.
Slide54Presentation: systemic HIV-related NHL
Advanced disease
Bulky
lymphadenopathy
Gastrointestinal
Fever, diarrhea, weight loss, perianal pain, bleeding, obstruction
Hepatic
Pain,
LFTs, biliary obstruction
Pulmonary
Mass lesion, pleural effusion, consolidation, infiltrates
Bone Marrow
Cytopenia
, weakness, fatigue, infection, bleed
CNS:
lymphomatous
meningitis
HA, radicular pain, back/neck pain, focal weakness, sensory loss, cranial nerve palsies
Diamond C, et al. Cancer. 2008;106(1):128.
Klatt
, EC, et al. Arch
Pathol
Lab Med. 1994;118(9):884.
White DA.
Clin
Chest Med. 1996;17(4):755.
Straus DJ. Med
Clin
North Am. 1997;81(2):495.
Slide55Evaluation: systemic HIV-related NHL
Biopsy
Excisional lymph node biopsy
GI tract
Upper/lower endoscopy
Imaging: CT
Biopsy
Pulmonary
Lung biopsyImaging: CXR/CTCNSNeuroimaging: MRI brain/spineCSF: lumbar puncture
Bottles K, et al. Ann Intern Med. 1988;108(1):42
Redvanly
RD, Silverstein JE.
Radiol
Clin
North Am. 1997;35(5):1083.
.Eisner MD, et al. Chest 1996;110(3):729.
Slide56Treatment: systemic HIV-related NHL
Antiretrovirals
OI prophylaxis: PCP, MAI
Chemotherapy
Rituximab
High-dose chemotherapy with autologous bone marrow transplant
Re A, et al. Blood. 2009;114(7);1306.
Mounier
N, et al. Blood. 2006;107(10;3832.Volberding PA, Baker KR, Levine AM, Hematology Am Soc
Hematol
Educ
Program. 2003:
294-313.
Barta
SK. Blood. 2013;122(19):3251-62.
Slide57Case: lymphoma
38
yo
AA female
Diagnosed with lymphoma and AIDS concurrently 3 years ago
Lymphoma treated and complete remission
VL undetectable >2 years
CD4 650Presents with fever, generalized
lyphadenopathy and inner thigh cellulitis
Slide58Case: lymphoma
Admitted for treatment
of infection
Lymphoma relapse
Chemotherapy
Slide59Summary
Cytopenias
are common in HIV-infection
Many causes
Treatment includes
antiretrovirals
Increased risk of VTE is present in HIV-infection
HIV-associated NHL is an AIDS-defining malignancy3 main types of NHL with many presentations and manifestations