W2-L5; VIRUSES AND HEMAPOIETIC STEM CELLS

Question 1

The subset of cells from which all other blood cells are formed are referred
to as

Answer 1

haematopoetic stem cells (HSCs) and progenitor cells

Question 2

Features of HSC

Answer 2

• Self‐renewal capacity
• and the ability to regenerate all the different cell types that comprise the blood‐forming system

Question 3

Two waves of hemapoiesis along the development of mammals

Answer 3

• Premitive: early embryogenesis
  *Initiated in the yolk sac

-Definitive: Late foetal stages
*Initiated within intra-embryonic sites
*Aorta-gonad-mesonephros (AGM)
*Foetal liver
*Bone Marrow

Question 4

What are the 2 ways that viruses use to affect HSCs proliferation, differentiation?

Answer 4

• Viruses act directly:
  -Direct infection of HSCs
  *Viral recognition (immune cells in the marrow see the virus and hamper it action)
• or indirectly:
  -Production of pro-inflammatory cytokines
  *Changes in the microenviroment

Question 5

What’s the underlying mechanism leading to pancytopenia?

Answer 5

• reduced production or
• increased destruction

Question 6

Definition of aplastic anaemia is____

Answer 6

Bone marrow failure with
pancytopaenia in the absence of bone marrow infiltrative
disease

Question 7

Pancytopenia

Answer 7

Decrease in all three blood cell types: red blood cells (anaemia), white blood cells
(leukopaenia), and platelets (thrombocytopaenia)

*Clinically may be asymptomatic or symptoms may related to the affected blood
line

Question 8

T/F:
Pancytopenia caused by the viruses is usually transient and reversible with resolution of the infection

Answer 8

TRUE

Question 9

Two forms of aplastic anaemia

Answer 9

-Acquired: Is immune
mediated in most cases; autoreactive lymphocytes mediate the destruction of
haematopoetic stem cells

• Congenital

Question 10

Can result from direct or
indirect destruction of haematopoietic stem/
progenitor cells

Answer 10

Acquired Aplastic anaemia

Question 11

What is the pathological hallmark of aplastic anaemia?

Answer 11

Hallmark pathologically is
peripheral pancytopaenia and an ‘empty’ bone marrow

Question 12

Haemophagocytic lymphohistiocytosis (HLH)

Answer 12

Clinical syndrome which cover a range of hyperinflammatory conditions which include viral-associated haemophagocytic syndrome, macrophage
activation syndrome and cytokine-release syndrome.

Question 13

Features of HLH

Answer 13

• Rare and life-threatening with multi-organ involvement
• Has a variety of
  triggers, both genetic and environmental.
• HLH may be congenital or
  acquired

Question 14

How do you know its HLH? What characterises it?

Answer 14

• haemophagocytosis in bone marrow, liver, or lymph nodes
• splenomegaly
• pancytopenia
• hyperferritinaemia (vry high ferritin)
• Fever

Question 15

What is the pathological hallmark of HLH?

Answer 15

• prolonged and excessive activation of immune cells particularly; natural killer, cytotoxic T-lymphocytes and
  macrophages in response to a trigger

Question 16

What triggers both the primary and secondary HLH?

Answer 16

Infectious agent

*Viruses are a common trigger ~35% of adults

Question 17

Two viral infection that account for 62% of reported viral cases of HLH in adults

Answer 17

EBV and CMV account for
62% of reported viral cases of HLH in adults

*Clinically, HLH may mimic acute viral disease

Question 18

Leading cause of infection-associated HLH

Answer 18

EBV

*Without early and
effective therapy, EBV-HLH has a high mortality rate

Question 19

Describe the EBV epidemiology

Answer 19

Epidemiology
* Gamma human herpes virus-4
* Ubiquitous, worldwide distribution
* Transmission, direct contact with oropharyngeal secretions

Question 20

Describe EBV pathology

Answer 20

Pathogenesis
* Primary infection following latency and periodic reactivation from B-cells.
- Disease profile is host-dependent, and varies in different population groups

Question 21

EBV-HLH can be due to:

Answer 21

• It’s secondary to EBV infection, in apparently EBV-immune individuals
• EBV infection in genetically predisposed for lymphoproliferative disease
  (BIRC4 or SHD21A), usually males (X-linked lymphoproliferative
  syndrome)
• Chronic active EBV infection
• Aggressive NK cell leukaemia, and T/NK cell lymphoma

Question 22

Has similarities to, and may
mimic secondary HLH

Answer 22

Clinical presentation of moderate-severe COVID-19

Question 23

(Within the Immunopathology of COVID-19)

Has a key role in
subsequent inflammatory response and organ injury

Answer 23

uncontrolled macrophage and monocyte activation due to a
dysfunctional interferon response to SARS-CoV-2 infection

Question 24

Discuss the epidemiology of pavovirus

Answer 24

Parvovirus B19 is ubiquitous and has a worldwide distribution
* Transmission routes:
* Vertical transmission
* Horizontal transmission-respiratory and transfusion mediated

Question 25

Discuss the pathogenesis of pavovirus

Answer 25

• Targets mostly Erythroid progenitor (pro-erythroblasts) and less megakaryocytes
• P-antigen (globoside) receptor and co-receptors
• Direct cytolytic affect of susceptible cells, leading to interruption of haematopoesis
• Chronic persistent infection in immunocompromised patients

Question 26

List the hematological manifestations of Pavovirus 19

Answer 26

• Pure red cell aplasia (Red cells reduced in numbers)
• Transient aplastic crisis
• Persistent anaemia
• Hydrops foetalis / Congenital anaemia (abnormal accumulation of fluid in at least two fetal compartments, such as the abdomen, chest, or under the skin)
• Other rare haematological syndromes
  *Thrombocytopenia
  *Neutropenia
  *Haemophagocytic syndrome

*Haematological manifestations of Parvovirus B19 are host-dependent, based on immune
status

Question 27

Discuss the epidemiology of cytomegalovirus

Answer 27

Epidemiology
* Ubiquitous
* Asymptomatic in immunocompetent individuals
* Severe disease in immunocompromised

Question 28

Discuss the pathogenesis of cytomegalovirus

Answer 28

Pathogenesis
* Mediate myelosuppression from lytic infection

Question 29

CMV management

Answer 29

In transplant pts
*Presumptive therapy – viraemia is detected
*Note: viraemia is a strong predictor of CMV ds
* Treatment: Ganciclovir

• AIDS pts
  *HAART to improve immune suppression
  *Be watchful for IRIS

Question 30

List the cytomegalovirus hematological syndromes

Answer 30

Haematological syndromes
* Thrombocytopaenia- congenital infection,severe thrombocytopenic purpura in 10-15% symptomatic babies
* Leukopaenia
immunocompromised hosts
* Pancytopaenia-Ganciclovir, guanosine analogue for CMV treatment and prophylaxis
* Leukocytosis-Infectious mononucleosis

Question 31

CMV diagnosis

Answer 31

Diagnosis
* CMV serology
* CMV PCR

Question 32

Impact of HIV-1 and HTLV-1 infection on hematopoietic and progenitor cells

Answer 32

• deregulation of normal haematopoiesis
• Development of leukaemia/lymphoma

Question 33

What’s the haematological Disease associated with HIV-1?

Answer 33

• Cytopaenias are the most common haematological abnormality affecting ≥1
  cell lineage
• They are a direct or indirect effects of HIV
• The severity and prevalence of cytopaenias are associated with disease stage, and generally improve with ART

Question 34

Clinical and Diagnostic Approach of retroviruses

Answer 34

1. History
   *Symptoms
   *Familial
   *Preceding/concurrent illness
2. Examination
3. Investigation
   * Initial Investigation
   * Full Blood Count with peripheral smear

• Additional
  *Biochemistry
  *Viral Studies (HIV serology, EBV serology,ParvoB19 serology and PCR, viral hepatitis serology,
  CMV studies, SARS-CoV-2 PCR)
  *Bone Marrow
  *Auto-immune studies
  *Nutritional studies