Can Certain Blood Pressure Medications Decrease Hematocrit?

ARBs, or Angiotensin II Receptor Blockers, are a class of medications primarily used to treat high blood pressure (hypertension). They also play a role in managing heart failure and protecting kidney function, particularly in patients with diabetes. ARBs work by blocking the effects of angiotensin II, a hormone that causes blood vessels to constrict, thus allowing blood vessels to relax and blood to flow more easily.


Mechanism of Action:

ARBs prevent angiotensin II from binding to its receptors on blood vessels and other tissues. This prevents the blood vessels from constricting, leading to lower blood pressure.

Common Uses:

1. High Blood Pressure: ARBs are a common first-line treatment for hypertension.
2. Heart Failure: They can help improve heart function and reduce symptoms of heart failure.
3. Diabetic Nephropathy: ARBs can help protect kidney function in people with diabetes.
4. Post-Heart Attack: They may be prescribed after a heart attack to reduce the risk of future cardiovascular events.

Examples of ARBs:

1. Losartan (Cozaar)
2. Valsartan (Diovan)
3. Candesartan (Atacand)
4. Irbesartan (Avapro)
5. Telmisartan (Micardis)
6. Olmesartan (Benicar)

ARBs and Hematocrit: What Human Studies Show

Key take-away

· Across very different clinical settings—hypertension, chronic kidney disease, kidney transplantation, heart failure, and “real-world” primary-care populations—use of an angiotensin-II receptor blocker (ARB) is consistently followed by a small but reproducible fall in hematocrit (and hemoglobin/RBC count).

· The effect is detectable within 4–8 weeks, reaches −1 to −3 vol % on average, and can persist for at least 12 months if treatment continues.

· Magnitude varies with dose, drug exposure time, baseline erythrocytosis, and concomitant ACE-I use.

· Proposed mechanisms: reduced renal EPO production (via relief of efferent-arteriole hypoxia), direct inhibition of AT-1–mediated erythroid progenitor growth, and blunting of HIF-1α/VEGF signaling.

1 Prospective or randomized trials

​

Population (N)	ARB / regimen	Follow-up	Mean ↓ hematocrit (or Hb)	Notes
Non-diabetic hypertensive albuminuric pts (245)	Olmesartan 40 mg daily (ESPECIAL trial)	8 wk	Hb −0.3 g/dL; correlated with ↓ albuminuria[1]	No change in eGFR; EPO also fell
CKD stage 3–4 diabetics (127)	Irbesartan 300 mg vs placebo	12 mo	Hb −0.7 g/dL vs −0.2 g/dL (p < 0.05)[2]	ACE-I-free background
Heart-failure outpatients (92)	Candesartan up-titrated to 32 mg	6 mo	Hct −2.4 vol % (baseline 40.8%) [3]	Parallel rise in serum K⁺
Kidney transplant recipients with post-Tx erythrocytosis (35)	Valsartan 80 mg	6 mo	Hct −4.6 vol % (from 50% to 45.4%) [4]	Corrected erythrocytosis in 74%

2 Retrospective database & “real-world” studies

​

Data set	Design	ARB exposure	Result
Nihon Univ. CDW, Japan (601 new ARB vs 601 CCB)	Propensity-matched, 12 mo lab comparison	Candesartan/valsartan/losartan/olmesartan/telmisartan monotherapy	ARB users: Hct −0.7%, Hb −2.9 g/L vs CCB −0.3%, −1.7 g/L (p < 0.01)[5]
Israeli HMO registry (≈100 k starters)	1-yr Hb pairs; adherence stratified	High-adherence ARB starters: OR 1.48 for incident anemia (WHO cut-points)[6]
Turkish tertiary center (454)	Hb before/after 6–12 mo	Mean Hb drop ACE-I −0.29 g/dL vs ARB −0.53 g/dL (p < 0.001)[7]
Danish nation-wide cohort (ACE-I/ARB stop study)	Patients who discontinued RAS blockers	Hb rose by +0.9 g/dL within 3 mo of discontinuation[8]

3 Special situations

· Polycythemia vera or secondary erythrocytosis: case series show valsartan or losartan normalise hematocrit when phlebotomy insufficient, supporting dose-dependent suppression of erythropoiesis.
· Myelodysplastic syndrome: discontinuing ACE-I/ARB improved Hb by +1 g/dL at 12 mo, implying the drugs had been contributory[8].

4 Magnitude and timeline

· Early phase (≤2 mo): average hematocrit drop 0.5 – 1 vol % (≈0.2–0.4 g/dL Hb).

· Chronic use (6–12 mo): cumulative fall approaches 1 – 3 vol % (0.6–1.2 g/dL Hb); greater in kidney-transplant erythrocytosis and high doses.

· Reversal occurs within 8–12 weeks after drug withdrawal in most reports.

5 Proposed biological basis

1. Ang II normally constricts efferent arterioles → mild cortical hypoxia → HIF-1α stabilization → EPO transcription. ARB lifts this hypoxic stimulus, lowering EPO release[1].

2. Ang II acts as a growth factor for BFU-E/CFU-E colonies through AT-1 receptors; losartan blocks this effect in vitro and in vivo[9].

3. Decreased VEGF and oxidative stress after ARB may further blunt marrow drive and parallel reductions in albuminuria, explaining the ESPECIAL correlation[1].

6 Clinical implications

· Monitoring: check CBC at baseline and again 4–8 weeks after starting an ARB, especially in patients with borderline Hb, CKD, heart failure or on dual RAS blockade.

· Polycythemia management: ARBs can be therapeutically used to trim hematocrit in post-transplant erythrocytosis or androgen-related polycythemia.

· Anemia risk: falls are modest, but in elderly or CKD patients may unmask iron deficiency or exacerbate ESA hyporesponsiveness.

7 Knowledge gaps

· Head-to-head comparisons among individual ARBs are scarce; whether telmisartan or azilsartan differ from losartan or valsartan on erythropoiesis is unknown.

· Long-term (>2 yr) hematocrit trajectories and interaction with SGLT2 inhibitors or GLP-1 RAs need study.

· Mechanistic work in humans linking ARB dose, renal oxygenation (BOLD-MRI), and EPO output is still missing.

Citations

[5] Cardiovasc Diabetol 2012;11:53.
[1] PLoS One 2015;10:e0128632.
[6] QJM 2013;106:925-33.
[2] Am J Hypertens 2008;21:317-22.
[3] Circulation 2001;103:904-7.
[8] Ther Adv Hematol 2021;12:2040620720958299.
[4] Transplant Proc 2004;36:134-6.
[9] Hypertension 2007;50:638-44.
[7] Turk J Med Sci 2021;51:1843-50

1. https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0128632
2. https://academic.oup.com/ajh/article/21/3/317/102314
3. https://www.ahajournals.org/doi/10.1161/01.cir.103.6.904
4. https://pubmed.ncbi.nlm.nih.gov/15866681/
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC3416676/
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC3547548/
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC10734815/
8. https://journals.sagepub.com/doi/10.1177/2040620720958299
9. https://academic.oup.com/qjmed/article/108/11/879/1904330

 

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Recently I had a really bad cold with a severe cough. It was so bad my doc put me on a bunch of stuff to reduce inflammation in my Bronchial and some cough trigger pills. He also had me stop using Lisinopril. It's one side affect in a drip and cough. I didn't take Lisinopril for BP, I toke it for migraines. So once my cold died and my cough settled he put me on Losartan(ARB). It's very similar to Lisinopril but the process in which it relaxes the blood vessels is a little different. Well today I went in for my 2 month blood donation. Well my hemoglobin was 15. It hasn't been that low since...

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Researchers conducted a controlled trial with 63 healthy adults (average age ~42, roughly half women). Each person did two test sessions—once taking valsartan (a medication that blocks angiotensin II type 1 receptors, called AT₁) and once taking a placebo (calcium carbonate), in random order. They took the pills about 4 hours before cycling moderately for 1 hour. Blood tests and heart function measures were taken before, during, and after exercise.


️ What They Found

• Blood pressure went down during exercise when taking valsartan—this effect was seen in both men and women.
• Heart chamber sizes (left atrium and ventricle) were smaller during exercise on valsartan compared to placebo, especially in men.
• Exercise performance (measured by peak oxygen uptake and how well the body extracted oxygen) did not differ whether participants took valsartan or placebo.

Key Finding: EPO (Erythropoietin) Response

• After exercise, blood levels of erythropoietin (EPO)—a hormone that stimulates red blood cell production—rose significantly in the placebo condition, but this rise was completely blocked when participants took valsartan.
• Likewise, exercise-induced changes in hormones that regulate EPO—such as angiotensin II, aldosterone, and copeptin—were dampened with valsartan.
• These results applied equally to men and women

What It Means in Simple Terms

• Typically, exercising triggers a hormonal signal—led by angiotensin II—that tells the body to make more EPO, helping build more red blood cells and boost endurance.
• When that signal is blocked by a medication like valsartan, it prevents the normal rise in EPO after exercise.
• So, while valsartan still lowers blood pressure (as expected), it also shuts down a hormonal adaptation that helps improve aerobic capacity over time.

Bottom Line


Taking AT₁-blocking medications like valsartan abolishes the usual increase in erythropoietin seen after exercise in healthy men and women. This suggests that some blood pressure medications may limit important hormonal responses to exercise, potentially affecting adaptations that normally help improve endurance.


Source: Blockade of angiotensin II receptor type 1 abolishes the erythropoietin response to exercise - PubMed