Septicemia resulting from bacterial sepsis can progress to hemolytic anemia and may be fatal if not identified promptly
Editors:
- Dr. Praful B. Godkar (Ph.D)
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD. - Dr. Gauri Kulkarni MD (Pathology)
Vice President, AGD Biomedicals (Pvt) LTD.
Acute hemolytic anemia resulting from bacterial septicemia may lead to fatal outcomes, if not diagnosed early(1). The vast majority of clinical manifestations are often mistaken for routine common infections. Hemolytic anemia accounts for about 5% of all documented cases of anemia(2). It presents with a variety of consequences, extending from mild symptoms to serious, potentially life-threatening systemic effects(2). Treatment of hemolytic anemia depends on the type and cause of the hemolytic anemia(2). Prompt ordering a Complete Blood Count (CBC) in patients experiencing prolonged fever, fatigue, chills, and headache can help diagnose hemolysis associated with bacterial septicemia(2,3,8). Identifying patients at increased risk of bacterial sepsis is crucial. CBC performed in 2 minutes on indigenous AGD HT 340 based on cutting-age technology can be useful in the fast detection of acute hemolytic anemia(8).
Q1. What is hemolytic anemia?
ANS: Hemolytic anemia occurs when red blood cells (RBCs) are abnormally destroyed for varied reasons(7). In hemolytic anemia RBCs are destroyed at rapid rate than the normal RBC cells formed from bone marrow which can replace them. Lifespan of RBCs are 100–120 days. In hemolytic anemia, a shortened RBC lifespan reduces the oxygen-carrying capacity of blood to body cells.
Q2. What are the various reasons that lead to rapid destruction of RBCs?
ANS(2,8) :The reasons for rapid destruction of RBCs can be Acquired (Extrinsic) or Inherited (Intrinsic)(7).
Q3. What are the Acquired (Extrinsic) conditions that lead to hemolysis of red blood cells?
ANS(2,8): In Acquired (Extrinsic) conditions normal RBCs are destroyed by the following various external factors:
(a) The antibodies and complement attaches to Rbcs leading to its destruction causing Autoimmune Hemolytic Anemia (AIHA)
(b) Due to severe viral or bacterial Infections
(c) Due to the direct action by certain drugs and chemicals
(d) Due to Incompatible blood transfusion
(e) Mechanical damage of RBCs, due to turbulent blood flow in certain events (Cardiac hemolytic anemia).
(f) Thermal injury
Q4. What are the Inherited (Intrinsic) conditions that lead to hemolysis of red blood cells?
ANS(2,8): Inherited conditions that cause red blood cell hemolysis, result from:
(a) Inherited defects in RBC membrane that affect the shape, and flexibility of RBC making them fragile. Eg: *Hereditary spherocytosis, which is caused by defective membrane proteins such as spectrin, resulting in spherical red cells that are easily trapped and destroyed in the spleen. *Hereditary Elliptocytosis (HE): RBCs formed in bone marrow are elliptical or oval in shape and prone to increased destruction.
(b) Defective globin synthesis : It Leads to abnormal hemoglobin structure. Examples include thalassemias and sickle cell anemia. These conditions result from decreased or absent synthesis of hemoglobin chains, leading to the formation of abnormal and fragile red blood cells.
(C) Deficiency of RBC enzymes (Enzymopathies). This reduces ability of red blood cells to handle metabolic stress. Examples: *Glucose-6-Phosphate Dehydrogenase deficiency: Synthetic defects in RBCs lead to oxidative damage of RBCs. *Pyruvate Kinase (PK) Deficiency: Affects energy production, in the form of ATPs and make cells vulnerable to stress.
Q5. What are the symptoms of Hemolytic anemia?
ANS: Symptoms of hemolytic anemia are listed in the following table:
TABLE 1(8)
| SR. NO. | SYMPTOMS | REASONS |
| 1 | Weakness and fatigue: | Due to low oxygen levels |
| 2 | Jaundice: | By a buildup of bilirubin from destroyed cells. |
| 3 | Reddish brown-colored urine: | Resulting from excretion of hemoglobin and its metabolites |
| 4 | Tachycardia: | Increased pumping of heart to compensate for low oxygen. |
| 5 | Dizziness: | Exertion due to lack of oxygen supply to cells of the body |
| 6 | Enlarged spleen: | Spleen functions streniously to filter out destroyed RBCs. |
| 7 | Enlarged liver: | Liver functions harder to cope up with low hemoglobin |
NOTE : It is necessary to diagnose patients with hemolysis related to sepsis, caused by microbial infection or by other factors, for effective treatment.
Q6. What are various infectious diseases that led to hemolysis of RBCs, explain with examples and related reasons?
ANS(8): The examples of microbial infections that lead to hemolysis of red blood cells are as follows:
(A) By direct action of microorganism on red blood cells and causing them to rupture: Examples: Infectious diseases such as malaria (Caused by Plasmodium parasites), Bartonella (Caused by Bartonella bacilliformis bacteria), Babesia (A tick-borne disease caused by Babesia protozoa),
(B) Bacteria that produce toxins, like hemolysins, can damage red blood cell membranes, causing hemolysis. Examples: *Clostridium perfringens infection, which produces an alpha-toxin that act on the RBC membrane, leading to rapid, life-threatening intravascular hemolysis. *Escherichia coli which secrete Shiga Toxin that cause Hemolysis of red blood cells.
(C) Microbial infections that prompt the immune system to create antibodies which destroy RBCs: Examples: *Mycoplasma pneumoniae (cause activation of antibodies that react with RBCs at lower temperatures (cold agglutinin disease), leading to hemolysis).*Syphilis (associated with Paroxysmal Cold Hemoglobinuria (PCH), leading to severe immune-mediated hemolysis.
CASE STUDY
A 59-year-old female with a history of type 2 diabetes mellitus presented with high-grade fever for past 3 days (1020 C) along with severe cramping abdominal pain, nausea, and vomiting. The urine specimen obtained exhibited a reddish coloration. Blood collected in EDTA tube appears hemolyzed. Her Complete Blood Count (CBC) report was as follows:
COMPLETE BLOOD COUNT
| TEST | RESULT | NORMAL RANGE |
| Hemoglobin | 8.3 g/dl | 13–18 g/dl |
| Total erythrocyte count | 5.2 X 1012 /l | 5.0 ± 0.5 X 1012 /l |
| Total leukocyte count | 21 X 109/l | 7.0 ± 3.0 X 109/l |
| Differential leukocyte count | ||
| Neutrophils | 38% | 40–75% |
| Lymphocytes | 52% | 20–45 % |
| Eosinophils | 2% | 1–4 % |
| Monocytes | 1% | 2–8 % |
| PCV | 30% | 36–48% |
| MCV | 64 fL | 82–92 fL |
| MCH | 27 pg | 27–32 pg |
| MCHC | 32% | 32–36 % |
| RDW-CV | 22.0 | 12–14 |
| Platelet count | 230 X 109/l | 150–400 X 109/l |
| Metzer Index (MI) | 12.30 | > 13 |
Stained blood smear Microscopic observations:
Peripheral blood smear examination revealed RBC showing anisocytosis with predominant spherocytes, elevated white blood cells with lymphocytes, and vacuolated neutrophils.
INTERPRETATION
Significant decrease in hemoglobin, decreased MCV, presence of anisocytes spherocytes, presence of hemoglobin in urine and blood indicate Hemolytic anemia. Elevated white blood cells and vacuolated neutrophils suggest a severe bacterial infection.
NOTE
Based on the case history and the CBC report, Stool culture test was recommended. The following are the corresponding findings from these reports:
Gram staining observations: The presence of large numbers of rod-shaped Gram positive bailli without spores.
Motility test: Non-motile organisms
With reference to Gram staining report and motility test the following the following two Culture media were used to observe culture characteristics of the bacteria :
(A) Blood agar: Quick growth under anaerobic conditions at 37°C.
Bacterial Colony Morphology: Formation of round, convex, smooth and glistening yellowish-grey colonies.
Color and Texture: The bacterial colonies typically appeared as translucent, grayish to yellow-gray formations with distinctive “dew-drop” characteristics with the presence of two concentric zones of hemolysis around the colonies:
(B) Tryptose Sulfite Cycloserine (TSC) Agar: Black to grey-colored colonies.
Biochemical reactions of the isolated Bacteria:
Methyl Red (MR), Nitrates, and H2S: Positive
Lecithinase: Positive
Litmus milk test: Positive
Nagler reaction: Positive
Interpretation:
Presence of Clostridium perfringens bacteria
Q7. Why does Clostridium perfringens cause red blood cell hemolysis?
ANS: Red blood cell (RBC) hemolysis during Clostridium perfringens infection takes place primarily by the action of following two potent toxins secreted by the bacteria: The alpha-toxin (CPA) and the perfringolysin O (PFO), which directly act on cell membrane of RBCs leading to their destruction.
NOTE
(1) It was possible to diagnose Hemolytic anemia and related cause by the prompt determination of CBC report and further study of bacteria and effective treatment with appropriate antibiotics.
(2) No need to use chemical tests based on specific biochemical reactions, if any available chromogenic media is used for bacterial culture such as CHROMAGARTM C. perfringens media. This media produces intense yellow colored colonies, using specific nutrients, enzyme substrates and inhibitors (to prevnt the growth of other bacteria)8.
References
(1) Yu CW, Chang SS, Lai CC, et al. Epidemiology of emergency department sepsis. Shock. 2019;51(5):619–24. doi: 10.1097/SHK.0000000000001219. [DOI] [PubMed].
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(4) G. Rajendran, P. Bothma, and A. Brodbeck, “Intravascular haemolysis and septicaemia due to Clostridium perfringens liver abscess,” Anaesthesia and Intensive Care, vol. 38, no. 5, pp. 942–945, 2010.
(5) S.-T. Law and M. K. Lee, “A middle-aged lady with a pyogenic liver abscess caused by Clostridium perfringens,” World Journal of Hepatology, vol. 4, no. 8, pp. 252–255, 2012.
(6) C. C. van Bunderen, M. K. Bomers, E.Wesdorp, P. Peerbooms, and J. Veenstra, “Clostridium perfringens septicaemia with massive intravascular haemolysis: a case report and review of the literature,” Netherlands Journal of Medicine, vol. 68, no. 9, pp. 343–346, 2010
(7) Y. Shindo, Y. Dobashi, T. Sakai, C. Monma, H. Miyatani, and Y. Yoshida, “Epidemiological and pathobiological profiles of Clostridium perfringens infections: review of consecutive series of 33 cases over a 13-year period,” International Journal of Clinical & Experimental Pathology, vol. 8, no. 1, pp. 569–577, 2015.
(8) Godkar PB, Godkar DP. Textbook of Medical laboratory technology (4th edition, 2024), Bhalani Publishers, Mumbai. India.
