# Sickled Cells (DD-613)

> Sickle cell disease is a group of inherited red blood cell disorders caused by a mutation in the beta-globin gene, which helps make hemoglobin. According to the US National Heart, Lung, and Blood Institute (NHLBI), normal red blood cells are disc-shaped and flexible, so they move easily through large and small vessels. The mutation swaps a single amino acid, valine for glutamic acid, producing hemoglobin S. When hemoglobin S gives up its oxygen in the tissues, it links into long, rigid strands inside the cell. A 2019 review in the Annual Review of Pathology by Prithu Sundd and colleagues describes how these polymers stiffen and distort the cell. The sickled cells are inflexible and can stick to vessel walls, slowing or blocking blood flow. That starves nearby tissue of oxygen and can cause sudden episodes of severe pain, called pain crises. NHLBI also notes that sickle cells break apart early, lasting only 10 to 20 days compared with 90 to 120 for normal red cells. The body may not keep up, which leads to anemia. Other complications NHLBI lists include acute chest syndrome, stroke, eye problems and infections. The disease is autosomal recessive: a person must inherit the mutation from both parents. The FDA says it affects about 100,000 people in the US. Chicago physician James B. Herrick first described it in the medical literature in 1910. On December 8, 2023, the FDA approved the first cell-based gene therapies for it, Casgevy and Lyfgenia, for patients 12 and older. The footage is a medical animation of red cells flowing through a vessel, then sickled cells clumping.

- Department: Science (also Nature)
- First published: 2025-07-12
- Last updated: 2025-07-12
- Permalink: https://detailenjoyer.com/case/sickled-cells/
- Author: Marcus Easterling (DetailEnjoyer), The Detail Department

## On the timeline

- **Dec. 8, 2023**: The FDA approves Casgevy and Lyfgenia, the first cell-based gene therapies for sickle cell disease

Full timeline: https://detailenjoyer.com/timeline/?case=sickled-cells

## Quick facts

- **DD-613-F01**: Sickle hemoglobin forms rigid strands when it releases oxygen. _(Write-up · Exhibit B (Strands form))_
- **DD-613-F02**: Sickle cells last only 10 to 20 days, compared with 90 to 120 for normal red cells. _(Write-up · Exhibit D (Short-lived))_

## Write-up

One swapped amino acid, one bent cell. Sickle hemoglobin stiffens into strands when oxygen runs low.

1. **One swap**: A single amino acid change in beta-globin produces hemoglobin S.
2. **Strands form**: When hemoglobin S releases oxygen, it links into rigid strands that bend the cell into a sickle.
3. **Blocked flow**: Stiff, sticky sickle cells can slow or block blood flow, causing pain crises.
4. **Short-lived**: Sickle cells last 10 to 20 days instead of 90 to 120, which leads to anemia.
5. **Gene therapy**: On December 8, 2023, the FDA approved the first gene therapies for the disease.

## Related case files

- [Blood Watch (DD-649)](https://detailenjoyer.com/case/blood-watch/): Another case about blood flow in small vessels
- [Sclerotherapy (DD-597)](https://detailenjoyer.com/case/sclerotherapy/): Another case about blood vessels
- [Rosalind (DD-093)](https://detailenjoyer.com/case/rosalind/): I linked a case where a DNA change shapes a cell
- [Blood Destruction (DD-395)](https://detailenjoyer.com/case/blood-destruction/): I linked more blood cells

## Reel vs. record

- **Note**: 'Due to abnormal hemoglobin': the cause is a single amino acid swap (valine for glutamic acid) in beta-globin, inherited from both parents. The disease is autosomal recessive.
- **Note**: 'Under low oxygen': specifically when hemoglobin S has given up its oxygen in the tissues. The strands then form inside the cell and distort it.
- **Note**: 'Prone to clumping and blocking blood flow': NHLBI describes sickled cells as inflexible and sticky. They can stick to vessel walls and block flow, depriving tissue of oxygen.
- **Note**: 'Complications like anemia': the anemia comes mainly from sickle cells breaking apart early, after 10 to 20 days instead of 90 to 120.
- **Missing**: sickle cell disease affects about 100,000 people in the US (FDA), and the first gene therapies were approved on December 8, 2023.

## Video: Sickled Cells: One Swapped Amino Acid, One Bent Cell

- Duration: 32.3 s · Published: 2025-07-12
- File: https://detailenjoyer.com/assets/videos/DMAroPkNtb2.mp4

### Transcript

DID YOU KNOW? Normal red blood cells or RBCs, are flexible biconcave discs designed to efficiently carry oxygen from the lungs to tissues and return carbon dioxide for exhalation. Their shape and flexibility allow smooth passage through small blood vessels. In contrast, sickle cells are rigid and crescent-shaped due to abnormal hemoglobin that polymerizes under low oxygen, causing cells to deform. These sickled cells are less efficient at oxygen transport, prone to clumping and blocking blood flow, which leads to pain, tissue damage, and complications like anemia and organ injury. NOW YOU KNOW!

## Questions & answers

**Q: What is the abnormal hemoglobin in sickle cell disease called?**  
A: It forms rigid strands. _(Source: Write-up · Exhibit A (One swap) · Sundd, Gladwin & Novelli (2019), Pathophysiology of Sickle Cell Disease, Annual Review of Pathology; Wikipedia: Sickle cell disease)_

**Q: When does hemoglobin S form rigid strands?**  
A: In the tissues, where oxygen is delivered. _(Source: Write-up · Exhibit A (One swap) · Sundd, Gladwin & Novelli (2019), Pathophysiology of Sickle Cell Disease, Annual Review of Pathology; Wikipedia: Sickle cell disease)_

**Q: How long do sickle cells typically last?**  
A: Normal red cells last 90 to 120 days. _(Source: Write-up · Exhibit B (Strands form) · NHLBI (NIH): Sickle Cell Disease (archived overview, 2022); NHLBI (NIH): Sickle Cell Disease, Causes and Risk Factors; Sundd, Gladwin & Novelli (2019), Pathophysiology of Sickle Cell Disease, Annual Review of Pathology)_

**Q: Who first described the condition in the medical literature, in 1910?**  
A: A Chicago physician. _(Source: Write-up · Exhibit A (One swap) · Sundd, Gladwin & Novelli (2019), Pathophysiology of Sickle Cell Disease, Annual Review of Pathology; Wikipedia: Sickle cell disease)_

**Q: About how many people in the US have sickle cell disease?**  
A: Per the FDA. _(Source: Write-up · Exhibit A (One swap) · Sundd, Gladwin & Novelli (2019), Pathophysiology of Sickle Cell Disease, Annual Review of Pathology; Wikipedia: Sickle cell disease)_

## Sources

- [NHLBI (NIH): Sickle Cell Disease (archived overview, 2022)](https://web.archive.org/web/20220309204600/https:/www.nhlbi.nih.gov/health-topics/sickle-cell-disease)
- [NHLBI (NIH): Sickle Cell Disease, Causes and Risk Factors](https://www.nhlbi.nih.gov/health/sickle-cell-disease/causes)
- [Sundd, Gladwin & Novelli (2019), Pathophysiology of Sickle Cell Disease, Annual Review of Pathology](https://doi.org/10.1146/annurev-pathmechdis-012418-012838)
- [FDA: FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease (December 8, 2023)](https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease)
- [Wikipedia: Sickle cell disease](https://en.wikipedia.org/wiki/Sickle_cell_disease)

## Cite this case file

Easterling, Marcus. "Sickled Cells." The Detail Department (DetailEnjoyer), case file DD-613, last updated Jul 12, 2025. https://detailenjoyer.com/case/sickled-cells/