Mustard gas poisoning: Question : Should drugs to elevate the WBC and RBC level be used for mustard gas poisoning? Why??

1. Mustard gas poisoning
Question :
Should drugs to elevate the WBC and
RBC level be used for mustard gas
poisoning? Why??

2. To be discussed:
1. Clinical Findings of Mustard Gas
Intoxication.
2. Hematological effects of mustard gas .
3. Management.

3. by:
Major Dr Mohammadullah (totakhil
)
(Afghanistan)

4. Clinical Findings of Mustard Gas
Intoxication.
The picture of such a poisoning is characterized in the
beginning by a latent period ,between contact and the first
symptoms.
The mustard gas effects several organs like skin ,eyes ,respiratory
system and other Organs (Mustard gas also affects a number
of other organs and tissues because of its high solubility in
lipids. Therefore, several unspecific, general symptoms follow,
such as nausea, vomiting, abdominal pains, headache,
fatigue, apathy, diarrhea, weight loss, and tachycardia.
The majority of these symptoms are apparently caused by
damage to the gastrointestinal tract .
Also they are partly explained by the substance's effect on
the hematopoietic system. )

5.  Sulphur mustard is an alkylating agent. Alkylating agents bind
covalently to various nucleophilic molecules such as
DNA, RNA, proteins and components of cell membranes.
 DNA: Mustard gas causes cross linking of DNA strands. Alkylation
of DNA can result in the disruption of its function.
 RNA: Alkylation of RNA molecules can result in altered translation
and altered protein synthesis resulting in cell death.
 Proteins: Binding to proteins mainly with the thiol group of
cysteine produces structural changes which may alter the
normal physiology of the cell i.e. altered enzyme activity.
 Membranes: Mustard gas can either alkylate structural proteins
located in the cell membrane or induce lipid peroxidation which
may result in irreversible changes and cell death.

6. Hematological effects of mustard gas
The blood count may reveal anaemia and neutropenia four
days post exposure. In general, initial leukocytosis on the first 2
to 3 days after exposure is followed by leukopenia in severe
intoxicated patients.
Initial leukocytosis followed by leucopenia is a usual finding in
mustard gas poisoning and recovers within 14 days. Marked
leucopenia is a sign of sinister prognosis, leading to
overwhelming infection and multiple organ failure and death.
Acute: Early leukocytosis, followed by mild leucopenia. Severe
leukopenia, thrombocytopenia and erythropenia indicate
bone marrow depression.
Chronic: Bone marrow depression leading to leukemia.

7. Management discussion.
 General principles:
Management of mustard gas poisoning consists of decontamination and
symptomatic treatment. The importance of rapid and efficient
decontamination can not be overemphasized.
Biomedical analysis:
Full blood count, serum electrolytes, urea, protein levels. Arterial blood gasses
determination is indicated in case of pulmonary toxicity.
Culture of sputum and eye exudate.
Blood cultures where indicated.
Skin blisters may be aspirated and the fluid obtained analysed for thiodiglycol.
(Thiodiglycol is a Chemical Weapons Convention schedule 2 chemical used in the production of sulfurbased blister agents such as mustard gas. Thiodiglycol is also a product of the hydrolysis of mustard gas. It
can be detected in the urine of casualties)
The same estimation may be performed in blood and urine in order to
differentiate blistering produced by mustard gas from that produced by other
agents such as Lewisite. Contents of blisters are not toxic to attendants.

8. Life support procedures and
symptomatic/specific treatment
Maintain respiratory and circulatory function.
Replace extracellular fluid loss, electrolytes and
proteins. Blood transfusion is indicated in case of
bone marrow depression.
Symptomatic treatment
Antidote treatment: No specific antidote is
available.

9. • Bone marrow depression in severe intoxicated patients may
be seen as an irreversible consequence of mustard gas
poisoning.
• Granulocyte, platelet and red cell transfusions as well as
bone marrow transplantation have been recommended for
treatment of aplastic anaemia. The value of Granulocyte
Colony Stimulating Factor has not been assessed but may
be of use.
• Several independent scientists (Callaway & Pearce, 1958;
Fasth & Sorbo, 1973; Vojvodic et al., 1985) have shown that
cysteine, thiosulfate and other thiols reduce the toxicity of
sulphur and nitrogen mustards (Nitrogen mustards are used
in chemotherapy of malignant diseases).
• The use of thiols has been proposed in the treatment of
mustard gas poisoning, but has not been established.

10. •
•
•
•
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Numerous other supportive measures were used in treating
casualties from the Iran-Iraq war: H2 antagonists to prevent
stress ulceration.
Heparin has been used to prevent deep venous thrombosis.
A single large dose of methyl prednisolone (2 g) may prevent
general tissue damage.
Administration of Vitamins C, B12 and folate may be of use.
Haemodialysis and haemoperfusion have been suggested,
although there is no firm theoretical basis for such therapy.

11. Granulocyte colony stimulating factor
(G-CSF) for mustard-induced bone
marrow suppression.
 Source
Department of Internal Medicine (Hematology/Oncology Division), Naval
Hospital, San Diego, CA 92134-5000.
Abstract
The authors describe the development of a clinical protocol to treat mustard
gas-induced myelosuppression with granulocyte colony stimulating factor (GCSF), a hematopoietic growth factor.
 Limited clinical evidence suggests a significant role for mustard gas-induced
myelosuppression in the overall morbidity of mustard gas victims.
 Initial data from primates revealed that G-CSF could ameliorate neutropenia
following nitrogen mustard exposure.
 Exploiting the extensive oncologic experience with G-CSF, which
demonstrated its safety and absence of serious side effects the authors
developed a clinical protocol for use of this drug in potential mustard gas
victims in the Persian Gulf conflict.

12. Crystal structure of 3 molecules of human G-CSF
 Colony stimulating factor 3 (granulocyte)

. From PDB 1rhg

13. REFERENCE:
•"Clinical and Morphological Findings on
Mustard Gas [Bis(2-Chloroethyl)Sulfide]
Poisoning," Journal of Forensic
Sciences, JFSCA,
•Department of Internal Medicine
(Hematology/Oncology Division), Naval
Hospital, San Diego

14. Thanks