Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 10 Haematologic, Hepatic and Renal Conditions

Training on Clinical Care of HIV, AIDS and Opportunistic Infections

Unit 10Haematologic, Hepatic and Renal Conditions

Haematologic, Hepatic and Renal Conditions- 2

Learning Objectives

• List causes of anaemia, low WBC counts, and platelet counts associated with HIV infection;

• Describe treatment for the common causes of HIV-associated haematologic conditions, and;

• Describe the evaluation of liver and kidney dysfunction.


Blood Disorders

Haematologic, Hepatic and Renal Conditions- 3Training on Clinical Care of HIV, AIDS and Opportunistic Infections


Case Study

• Maggie, a 23 year old woman from Oshakati was diagnosed with HIV during her recent pregnancy. She and her baby each received a dose of nevirapine according to national guidelines.

• She is seen now, 2 months after the birth, to be assessed for HAART. Maggie reports little energy. When she carries her baby and other heavy items she is breathless and aware of her heart pounding.



Case Study (2)

• Maggie has no fever, no night sweats, and no cough

• She is not on any medication



Case Study: On Exam (3)

• T 37.5°C, Pulse 110, RR 24, BP 110/60

• Pale mucous membranes & hand creases

• No jaundice

• No jugular venous distention

• 2/6 systolic ejection murmur

• Chest clear

• No hepatosplenomegaly

• No peripheral edema



Case Study: On Exam (4)

• Hemoglobin 7.5 g/dl• MCV 75

• Reticulocyte count 0.3%• White Blood Count 3,600• Platelet count 210,000• Creatinine normal• ALT normal• RPR negative• Hepatitis B surface antigen negative• CD4 lymphocyte count 110 cells/cu mm



Degree of Anaemia

• Mild anaemia• Hb > 10 g/dl to normal

• Moderate anaemia• Hb 5 -10 g/dl

• Severe anaemia• Hb < 5 g/dl



Mild Anaemia

• Screen and investigate if:• Bleeding• Jaundice• Fever

• Supportive treatment• Re-enforce counselling on good nutrition • Nutritional support with daily

multivitamin/multimineral supplement

• Reassess for response in 1-2 months



Moderate - Severe Anaemia

• Evaluate for severity and a specific cause• History and physical

• Acute or chronic blood loss• Chronic cough• Weight loss• Tachycardia, breathlessness, fatigue• Fever• Jaundice• Lymphadenopathy• Hepatosplenomegaly• Liver or kidney disease



Laboratory Evaluation

• Laboratory testing may include:• FBC with RBC indices, reticulocytes• HIV test (if not done already)• In appropriate geographic regions

• Malaria smear• Stool for ova and parasites (hookworm)• Urine for Schistosoma eggs

• Chronic cough, fever or suspicion of TB• Sputum for direct microscopy

– Chest x-ray if smears for AFB negative



Laboratory Evaluation (2)

• If liver or kidney disease suspected• ALT / AST• Urea or creatinine

• Suspected ulcer disease in older patients with iron deficiency

• Stool for occult blood

• Consider tests for• Serum Iron / ferritin / TIBC• Serum Folate• Serum B12 levels



Severe Anaemia

• In case of a negative initial evaluation of severe anaemia:• Transfuse (if needed) after blood specimens

obtained• Bone marrow aspirate or biopsy

• TB or MOTT• Disseminated fungal infection• Malignancy• Other bone marrow condition



Anaemia Classification With Examples

B12, folate deficiency

haemolysis Macrocytic (MCV > 100)

anaemia of chronic disease

acute bleeding, haemolysis

Normal size

iron deficiency, chronic disease

chronic blood loss

Microcytic

(MCV < 80)

Inadequate Production

(low retics)

Loss or Destruction (high retics)

RBC Size

Process



Case Study: How would you Classify Maggie’s Anaemia So Far?

• Moderate (Hb=7.5 g/dl, so between 5 and 10)

• Microcytic (MCV=75, so <80)• Low reticulocyte count• Could be:

• iron deficiency – multiple causes• anaemia of chronic disease (nb: no

indication from initial investigations)



Microcytic Anaemia

• Chronic iron loss• Normal menstruation• Pregnancy• Hookworm• Schistosomiasis• Non-infectious GI tract bleeding

• Ulcer, gastritis, colon cancer

• Anaemia of Chronic Disease• Nutritional deficiency• Thalassaemia

• Congenital due to abnormal Hb synthesis



Comparison of Iron-deficiency and Anaemia of Chronic Disease

Laboratory parameters

Iron deficiency

Anaemia of chronic disease

MCV low usually normal;

15-25% low

Serum iron low low (or low normal)

TIBC high low (or low normal)

Serum ferritin low High or normal

RDW = (MCV/RBC)

high Normal (11-14.5%)



Normocytic Anaemia

• haemolysis – (before response activated)• Malaria• Autoimmune hemolytic anaemia

• Early iron deficiency anaemia• Chronic renal failure

• Decreased erythropoietin causes decreased RBC production

• Chronic liver disease• Endocrine disorders• Bone marrow disorders



Normocytic Anaemia (2)

• Anaemia of Chronic Disease • Reduced iron utilization for hemoglobin

production despite adequate iron stores• Chronic infections

• Advanced HIV• TB and MOTT

• Chronic inflammatory disease• Rheumatoid arthritis • Collagen-vascular disease

• Malignancy



Macrocytic Anaemia

• haemolysis• Young RBCs are large

• Malaria• Autoimmune hemolytic anaemia

• Folate or B12 deficiency

• Bone marrow disorders• Aplastic anaemia

• Myelodysplastic syndrome

• Some leukaemias

Note: AZT and d4T cause macrocytosis. If there is no anemia, it does not need to be evaluated.



HIV-Associated Anaemia

• Anaemia is: • the most frequent haematological abnormality

seen in patients with HIV• an independent predictor of all-cause mortality

and AIDS-related mortality; also associated with a more rapid decline in CD4 counts*

• often multifactorial in HIV patients*study in women with HIV in Tanzania: J. Acquir Immune Defic Syndr

2005;40:219-225



HIV-Associated Anaemia (2)

• Nutritional deficiencies complicated by malabsorption• Iron, Folate, B12 (?)

• Protein

• Anaemia of chronic disease• HIV, OIs, Malignancies

• Reduced erythropoietin production• Disordered iron utilization• Cytokine production decreases marrow output



HIV-Associated Anaemia (3)

• Specific OI• Parvovirus B19

• Marrow invasion• MOTT, TB, CMV, EBV, Lymphoma

• Medications• Reduced production

• AZT, (d4T)• Amphotericin• Trimethoprim, pyrimethamine• albendazole

• haemolysis in G6PD deficiency (Sulfa, dapsone)



Case Study (5)

• Factors likely to contribute to Maggie’s anaemia• Pregnancy

• Reduced iron stores• Possible reduced folate• Intra –partum or post-partum bleeding

• Possible role of parasitic infection• Malaria during pregnancy• Hookworm

• Advanced immunosuppression• CD4 110• Mild leucopoenia



Case Study: Maggie’s Lab Test Results

• Malaria smear: negative

• Stool parasite exam• Positive for hookworm

• Measuring serum iron and folate may be useful if available• Iron low, RDW high, serum ferritin low• Folate normal



Case Study: Treatment

• Maggie is treated for her hookworm with albendazole

• She receives supplemental iron & folate• She begins OI prophylaxis with

cotrimoxazole 960 mg daily• She begins isoniazid preventive therapy• She begins first line HAART with stavudine,

lamivudine and nevirapineNB: treating HIV patients with iron in the absence of iron

deficiency is not recommended



Case Study: Follow-up

• After 3 months of combined therapy, Maggie’s haemoglobin is 11 grams/dl



Summary: Management of Anaemia In Patients with HIV

• Classify the type of anaemia

• Correct the cause of the anaemia

• If iron deficiency, give iron after correcting the underlying problem

• Give HAART if anaemia is due to HIV• Unexplained anaemia <8 g/dl is a WHO

Clinical Stage 3 condition• Avoid AZT



HIV-Associated Leukopaenia and Neutropaenia

• Common with advanced immunosuppression• Direct bone marrow suppression in advanced HIV disease• CMV, EBV, parvovirus B19• Hypersplenism (TB, MAC)• Low lymphocyte count reflects reduction in CD4 cells

• Drug toxicity a common cause of leukopaenia• Zidovudine, tenofovir• Sulfa, trimethoprim, pyrimethamine• Ganciclovir

• 20-34% of HIV-infected will experience neutropaenia• Unexplained neutropaenia < 0.5 x 109/L is a WHO

Clinical Stage 3 condition



Thrombocytopenia

• About 11% of HIV-infected patients will develop a low platelet count (<100,000)• Up to 25-45% with advanced immunosuppression

• May be part of marrow suppression in advanced HIV with anaemia and leukopaenia

• Autoimmune• Immune thrombocytopenic purpura (ITP)

• With haemolysis• Malaria• Thrombotic thrombocytopenic purpura (TTP)• Disseminated intravascular coagulation (DIC)

• Drug toxicity: Ganciclovir, Ranitidine• Viral: Parvovirus B19



Immune Thrombocytopaenic Purpura (ITP)

• Antibodies against platelets or megakaryocytes• Bone marrow aspirate / trephine may help with diagnosis• Monitor platelet counts closely if >75,000 • If <75,000 (certainly < 20,000) and spontaneous bleeding

consider treating:• HAART if proven ITP

• Unexplained chronic platelets <50,000 is WHO Stage 3• Avoid AZT – marrow suppressive

• If does not remit, consider prednisone 30-60 mg/day• Intravenous immune globulin (IVIG) if available• Platelet transfusions in emergencies; most transfused

platelets will be destroyed so this is not a lasting solution



Thrombotic Thrombocytopenic Purpura (TTP)

• Rare but more common in HIV infected than in non-HIV infected

• Disseminated platelet aggregation• Syndrome

• Haemolytic anemia• Thrombocytopenia (thrombotic microangiopathy)• Fever• Acute renal failure• Altered mental status

• Many precipitating factors• HIV infection• Pregnancy• Medications• Bacterial toxins



Treatment• HAART• Support with platelet-depleted FFP for up to 3

weeks• Avoid platelet transfusions – may increase

thrombotic risk• Corticosteroids • Consider splenectomy if refractory• Daily plasmapheresis

• Not currently available in Namibia

• Vincristine for relapse

Thrombotic Thrombocytopenic Purpura (TTP) (2)


Liver Disease



Patterns of Liver Abnormalities

1. Haemolysis/Indirect Bilirubin

2. Acute hepatocellular necrosis

3. Chronic hepatocellular disorders

4. Alcoholic hepatitis & cirrhosis

5. Infiltrative Disease

6. Cholestasis



Liver Function Tests As An Aid In diagnosis

See Handout 11.1



Case 1

• 45 year old man presents to the clinic with jaundice, abdominal complaints and feeling “unwell”. He is HIV positive and has a CD4 count of 180.

• Laboratory test results:• Elevated direct > indirect bilirubin• AST=360 U/L, ALT=180 U/L• GGT=235 U/L• Alkaline phosphatase normal• Albumin = 25 g/L• PT prolonged



Case 1 (2)

• What is the most likely cause of his jaundice?

• Alcoholic hepatitis



Case 2

• 28 year old woman on HAART (d4T/3TC/NVP) presents very unwell with jaundice, high fever (39°C) and right-sided abdominal pain.

• Laboratory test results:• Elevated direct > indirect bilirubin• AST=405 U/L, ALT=650 U/L• GGT=normal• Alkaline phosphatase = 200 U/L• Albumin = normal• PT normal



Case 2 (2)

• What is the most likely diagnosis?

• Acute hepatocellular necrosis, probably infectious in origin (fever)

• What is the role of nevirapine in this case?



Case 3

• 36 year old woman on HAART presents with vague abdominal complaints. On examination she has hepatomegaly.

• Laboratory test results:• Bilirubin normal• AST and ALT normal• GGT=100 U/L• Alkaline phosphatase = 300 U/L• Albumin normal• PT normal



Case 3 (2)

• What pattern of liver injury does this probably represent?

• Infiltrative Disease



Case 4

• 25 year old man with malaise, fever and jaundice.

• Laboratory test results:• Indirect bilirubin high• AST = 65 U/L, ALT normal• All other liver tests normal



Case 4 (2)

• What is the most likely explanation for the jaundice?

• Haemolysis



Case 5

• 48 year old man with jaundice which he first noticed a few weeks ago.

• Laboratory test results:• Elevated direct > indirect bilirubin• AST=240 U/L, ALT=215 U/L• GGT=normal• Alkaline phosphatase = 200 U/L• Albumin = 26 g/L• PT mildly prolonged



Case 5 (2)

• What could be the cause of his jaundice?

• Chronic hepatocellular disorders



Case 6

• 30 year old man with jaundice, fever, and right upper quadrant pain. He has HIV and his CD4 count is 24.

• Laboratory test results:• Elevated direct bilirubin• AST=230 U/L, ALT=250 U/L• GGT=115 U/L• Alkaline phosphatase = 400 U/L• Albumin = normal• PT normal



Case 6 (2)

• What could be the cause of his jaundice?

• Cholestasis• cholangitis



CholestasisIntrahepatic Extrahepatic

Acute hepatitis (A, B, C, alcohol, EBV, CMV)

Cancer: pancreas, gall bladder, etc

Cirrhosis Enlarged portal lymph nodes

1° biliary cirrhosis

Anabolic and contraceptive steroids

antibiotics

Sclerosing cholangitis


Renal Disorders



Kidney Disease

• HIV-associated renal disease

• HIV-associated nephropathy

• Drug toxicity

• Kidney Stones

• Glomerulonephritis

• Acute renal failure

• Chronic renal failure



Quantify Renal Insufficiency

• Measure creatinine clearance with a serum creatinine and 24-hour urine collection for creatinine

• Estimate creatinine clearance with a serum creatinine and the formula:

=(140-age) x Lean Body Wt (kg) x 1.22 plasma creatinine (umol/l)

For women, multiply above by 0.85

Normal values: men 97-137 ml/min; women 88-128 ml/min



HIV-Associated Nephropathy (HIVAN)

• Rapidly progressive RF in HIV+ men• Rare in women

• Moderate-severe proteinuria

• Normal blood pressure, no edema

• No cells or casts in urine

• Enlarged, echogenic kidneys

• Pathology: Focal Segmental Sclerosing Glomerulonephritis (FSGN)



Treatment of HIVAN

• Avoid nephrotoxins

• May respond to HAART• Use doses of NRTIs adjusted for renal

insufficiency

• Progression may slow with treatment of proteinuria• Analogous to diabetic FSGN• ACE-inhibitors, calcium channel blockers



Renal Drug Toxicity

• A wide variety of drugs may injure the kidney via different mechanisms• NSAIDS• Aminoglycosides• Iodine containing contrast dye• Tenofovir• Amphotericin B



Membranoproliferative Glomerulonephritis

• Associated with Hepatitis C, HIV, and other conditions

• Presents as:• Nephritic syndrome with urinary RBC, RBC

casts, proteinuria, renal insufficiency, hypertension, edema

• Nephrotic syndrome with high grade proteinuria, low serum albumin, high cholesterol, edema

• Progresses to renal failure• No known therapy



Acute Renal Failure

• Often reversible• Many etiologies

• Decreased renal blood flow• Toxic injury• Urinary tract obstruction

• Immediate management• Ensure adequate blood volume and blood

pressure• Ensure bladder drainage



Acute Renal Failure (2)

• Evaluation• BUN, creatinine, electrolytes• Urine analysis• Review history for potential insults including hypotension

and drug or toxin exposure• Renal ultrasound?

• Ongoing management• Manage fluids and electrolytes• Minimize protein load• Avoid nephrotoxins• Dialysis



Chronic Renal Failure

• Irreversible

• Many etiologies• Diabetes

• Hypertension

• Glomerulonephritis

• Common syndrome• Azotemia, anaemia, acidosis, high phosphate

• Mild proteinuria

• Hypertension common

• Small shrunken kidneys



Renal Stones

• Many etiologies• Calcium• Urate • Indinavir stones

• Stones are crystals of precipitated drug• Occurs with high blood levels or dehydration• Stones often pass spontaneously with fluids and

analgesics• Intervention is rarely needed



Key Points

• HIV-associated anaemia is often multifactorial.

• Simultaneous treatment of factors contributing to anaemia is very effective.

• Characterizing the pattern of liver injury helps guide the workup and treatment of liver disease.

• HIV itself is one cause of renal insufficiency which may respond to HAART.


Documents

Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 10 Haematologic, Hepatic and Renal Conditions