Lecture 7.0 Pancytopenia 2024 Flashcards

Question

Ineffective hemopoiesis

Answer 1

- Failure to achieve adequate bone marrow output of mature haemopoietic cells- despite there being apparently normal/increased haemopoietic activity in the bone marrow- due to increased intramedullary cell death. * The haemopoietic precursors in the bone marrow are usually well represented but morphologically abnormal, and there is increased intramedullary cell death.

Answer 2

* Megaloblastic anaemia * Chronic infection –Most notably HIV and TB in South Africa * Drugs –Including folate antagonizing agents (such as Methotrexate) and drugs which interfere with DNA synthesis /repair (such as Nucleoside analogues (commonly AZT) and chemotherapeutic agents). * Myelodysplastic neoplasms (MDS) * Other miscellaneous causes – Multi-organ failure – Starvation

Answer 3

- Associated with an increased risk of acute myeloid leukaemia * Can occur at any age, but is much morecommon in the elderly. - Diagnosis is made on the basis of morphologic dysplasia in the bone marrow (>10% of the cells in one/more cell lines) in the absence of other causes * Cytogenetic abnormalities are present in 50-90% of cases (commonly del/monosomy(5q), del/monosomy(7q), trisomy 8 or a complex karyotype). * Somatic mutations in a variety of genes are also present in most cases.

Answer 4

- A clonal stem cell disorder (malignancies in the bone marrow) characterized by the presence of peripheral cytopenias as a result of ineffective haemopoiesis

Answer 5

In healthy people: – ~5% of the red cell mass – ~30% of all platelets – ~40% of marginating neutrophils are sequestered in the spleen. *If the spleen is enlarged, the proportion of each respective cell line pooled in the spleen may be increased

Answer 6

Hypersplenism is characterized by: – 1 or more cytopenia associated with enlargement of the spleen – The bone marrow is hypercellular – The life span of the sequestered cells tends to be attenuated (reduced) – The cytopenias recover following splenectomy * Usually, the cytopenias are mild/moderate. eg. It is unusual for the platelet count to be <50x10^9/l

Answer 7

HLH *Caused by a lack of normal downregulation of activated macrophages and lymphocytes, which results in excessive inflammation following an initially appropriate immune response

Answer 8

HLH is triggered by an incident which disrupts immune homeostasis. – Infection *Viral (EBV, CMV, HSV, VZV, Measles, HIV) *Bacterial (TB, GNB) *Parasitic (Leishmaniasis) – Lymphoma *Hodgkin *Non-Hodgkin (particularly T-cell neoplasms) – Autoimmune pathology (Macrophage activation syndrome)

Answer 9

HLH Clinical features * Most patients are acutely ill with multiorgan involvement * S&S related to cytokine excess –Persistent fever –Organ dysfunction (hepatitis, respiratory distress, renal dysfunction) * S&S due to accumulation of activated macrophages – Hepatosplenomegaly – Skin rashes – Neurological manifestations

Answer 10

* Cytopenias (due to haemophagocytosis) * Elevation of serum Ferritin (particularly worrying if >10 000 ug/L) * Deranged liver function * Coagulopathy (DIC, low Fibrinogen)- Impaired body's ability to coagulate or form clots * Hypertriglyceridemia * Haemophagocytosis on Bone marrow aspirate *HLH typically has a high mortality rate (50 – 100%), partly as a result of delayed diagnosis and treatment, it can mimic many other conditions in its early stages so it's missed

Answer 11

– Immunosuppressive Rx (high dose Corticosteroids) – Immunoglobulins (Ivig) – Etoposide (Topoisomerase inhibitor) – Treat the underlying trigger

Answer 12

* FBC with a differential white cell count and peripheral blood smear review * Reticulocyte count * Vitamin B12 and folate levels * Iron studies * HIV testing * Bone marrow aspirate and trephine biopsy (including samples for flow cytometry and cytogenetics) * Further investigation depending on the clinical context (such as liver function tests, other viral studies, testing for an underlying auto-immune disease etc)

Answer 13

Treatment of pancytopaenia 1) Specific management depends on the underlying cause 2) Supportive management: -Blood product transfusion -Neutropenic measures as infection prophylaxis -Growth factor support -Iron chelation therapy

Answer 14

Patients with severe neutropenia (Neuts <0.5x10^9/l) are at risk of life threatening sepsis (particularly in those patients without good bone marrow reserve). * General neutropenic measures: – Good dental hygiene to prevent oral infections and bacteraemia from an oral source. – Hand and food hygiene and strict aseptic technique for medical procedures – Isolation – Age-appropriate immunizations and annual influenza vaccines. – Isolation – Digital rectal examination, suppositories and enemas should be avoided

Answer 15

* Infection prophylaxis: – Patients should be closely monitored, and broad spectrum empiric antibiotics started at any sign of infection – Antibiotic prophylaxis with a fluoroquinolone where the neutrophil count is expected to be <0.5x10^9/l for >10 days. – Antifungal prophylaxis (oral Fluconazole)

Answer 16

1) drives proliferation and differentiation of neutrophil progenitor cells. 2) Accelerates neutrophil maturation

Answer 17

Not used universally in patients with neutropenia. * Used in patients with profound febrile neutropenia (neutrophil count < 0.1 x10^9/L) AND - Clinical signs indicating potential septic shock (such as hypotension, organ dysfunction etc) OR - Persistent pyrexia (elevated body temperature) despite appropriate antibiotics/ antifungals OR - Invasive fungal infection