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High Hematocrit: The Critical Dangers Unveiled

High Hematocrit: The Critical Dangers Unveiled

Did you know a hematocrit level above normal can mean health issues? These can range from dehydration to serious conditions like heart or lung disease.

A hematocrit test is part of a complete blood count (CBC). It measures the red blood cells in your blood. Understanding your hematocrit levels is key because they can show health problems if they’re off.

We’ll look into what high hematocrit levels mean, their causes, and what to do if your results are high.

Key Takeaways

  • Understanding hematocrit meaning is key for blood test results.
  • Hematocrit levels show the red blood cells in your blood.
  • A high hematocrit level can mean dehydration or serious health issues.
  • The hct blood test is a vital tool for doctors.
  • Knowing your hematocrit levels helps in early health issue detection and management.

Understanding Hematology Tests

Hematology tests are key for diagnosing and tracking many health issues. They look at the blood’s parts, giving us insights into our health.

What is a Complete Blood Count (CBC)?

A Complete Blood Count (CBC) checks the blood’s main parts: red blood cells, white blood cells, and platelets. It’s a common test in hematology.

  • Red Blood Cell (RBC) Count: Counts the RBCs, which carry oxygen.
  • White Blood Cell (WBC) Count: Counts the WBCs, important for fighting infections.
  • Platelet Count: Counts the platelets, key for blood clotting.

Key Components of Hematology Tests

Hematology tests, like CBC, give detailed info on blood components. Key parts include:

  1. Hematocrit (HCT): Shows the blood volume’s red blood cell part. It’s a key sign of oxygen transport.
  2. Hemoglobin: A protein in red blood cells that carries oxygen. Low levels can mean anemia.
  3. Red Blood Cell Indices: Show the size and hemoglobin in red blood cells. They help diagnose anemia types.
ComponentDescriptionClinical Significance
RBC CountNumber of red blood cellsIndicates anemia or polycythemia
WBC CountNumber of white blood cellsIndicates infection, inflammation, or leukemia
Platelet CountNumber of plateletsIndicates bleeding disorders or thrombocytopenia
Hematocrit (HCT)Proportion of blood volume occupied by RBCsIndicates dehydration, polycythemia, or anemia
HemoglobinProtein in RBCs that carries oxygenIndicates anemia or hemoglobin disorders

“Blood tests, like CBC, are key in checking a patient’s health and spotting many conditions, from anemia to leukemia.”

What is Hematocrit in Blood Tests?

High Hematocrit: The Critical Dangers Unveiled

The hematocrit test measures the volume percentage of red blood cells in the blood. It’s a key part of a complete blood count (CBC). It gives insights into the body’s red blood cell count.

Definition and Measurement of Hematocrit

Hematocrit is the ratio of red blood cells to total blood volume, shown as a percentage. It’s found through a CBC test. For men, it’s usually 40-54%, and for women, 37-48%. These numbers can change based on the lab and the person’s age and gender.

This test is important for spotting conditions like anemia or polycythemia. An abnormal hematocrit level can signal health problems, from dehydration to serious blood disorders.

Normal Hematocrit Ranges by Age and Gender

Hematocrit ranges differ by age, gender, and other factors. Men generally have higher levels than women. Adult men’s levels are between 40.7% and 50.3%. Adult women’s levels are between 36.1% and 48.3%.

Children and pregnant women have their own ranges, based on their specific conditions.

  • Adult Men: 40.7% to 50.3%
  • Adult Women: 36.1% to 48.3%
  • Children: Varies by age
  • Pregnant Women: Generally lower due to increased blood volume

Significance in Overall Health Assessment

Hematocrit is a key health indicator. It shows how well the body transports oxygen. An abnormal level can signal health issues, like dehydration, lung disease, or heart disease.

Healthcare providers use hematocrit to guide patient care. Regular CBC tests are vital for health and catching problems early.

High Hematocrit: Causes and Significance

Understanding why hematocrit levels are high is essential for proper treatment. Hematocrit shows how many red blood cells are in your blood. It’s a key measure of your health.

What Constitutes Elevated Hematocrit Levels?

Levels above 49% for men and 45% for women are usually high. These numbers can change based on the lab. High hematocrit levels mean you have more red blood cells. This can happen for many reasons.

Understanding high hematocrit is important. It helps us know why it’s happening and what it means for your health. Below is a table that explains more about high hematocrit levels.

CauseDescriptionClinical Significance
DehydrationReduced plasma volume due to fluid lossTemporary elevation, reversible with hydration
Primary Polycythemia (Polycythemia Vera)A bone marrow disorder leading to excessive red blood cell productionIncreased risk of blood clots and cardiovascular events
Secondary PolycythemiaCaused by external factors such as high altitude, smoking, or chronic hypoxiaVaries depending on the underlying cause

Primary vs. Secondary Polycythemia

Polycythemia means you have too many red blood cells. It’s divided into primary and secondary types. Primary polycythemia, or polycythemia vera, is when your bone marrow makes too many red blood cells. Secondary polycythemia happens because of things like high altitude or tumors.

Clinical Significance of High Hematocrit

High hematocrit levels can lead to serious problems. These include blood clots, heart disease, and more. It’s important to manage high hematocrit levels to avoid these issues.

Healthcare providers can create better treatment plans by understanding high hematocrit. This helps address the root cause and reduce risks.

Common Causes of High Hematocrit

High Hematocrit: The Critical Dangers Unveiled

High hematocrit can be caused by many things, from temporary dehydration to long-term blood disorders. Knowing what causes it is key to treating it right.

Dehydration as a Primary Cause

Dehydration is a big reason for high hematocrit. When we lose too much water, our red blood cells get more concentrated. This happens if we don’t drink enough, sweat too much, or have illnesses that make us vomit or have diarrhea. Drinking enough water is very important, even more so in hot weather or when we’re very active.

Polycythemia Vera and Other Blood Disorders

Polycythemia vera is a rare condition where the body makes too many red blood cells. This can make the hematocrit go up. It also raises the risk of blood clots and heart problems. Other blood disorders can also cause high hematocrit levels.

Lung and Heart Conditions

Chronic lung diseases like COPD and some heart conditions can make the blood have less oxygen. The body then makes more red blood cells, raising the hematocrit. Heart problems like congenital heart disease and heart failure can also cause it to go up.

Genetic Factors

Genetics can also affect hematocrit levels. Some genetic mutations can change how red blood cells are made or how the body handles oxygen. For example, some families might have a genetic condition that leads to high hematocrit.

Finding out why someone has high hematocrit is very important. We will work with doctors to figure out the cause and find the right treatment.

Environmental and Lifestyle Factors Affecting Hematocrit

Many environmental and lifestyle factors can change hematocrit levels, a key health indicator. Hematocrit shows the amount of red blood cells in the blood. Knowing these factors helps understand test results better.

High Altitude Living

High altitudes can change hematocrit levels. At higher places, there’s less oxygen, so the body makes more red blood cells. This can raise hematocrit levels. A hematology expert, says, “People living high up have more red blood cells to handle less oxygen.”

Smoking and Carbon Monoxide Exposure

Smoking affects hematocrit levels too. It introduces carbon monoxide, which harms red blood cells’ oxygen-carrying ability. This might make the body produce more red blood cells, raising hematocrit. Quitting smoking can help keep hematocrit levels normal and improve health.

Certain Medications and Supplements

Some medicines and supplements can also change hematocrit levels. For example, erythropoietin (EPO) boosts red blood cell production. It’s used to treat anemia but can be misused by athletes. Using EPO and similar substances should be done carefully under doctor’s guidance.

Dehydration and Fluid Balance

Dehydration can also impact hematocrit levels. Losing fluids makes red blood cells more concentrated, raising hematocrit. Drinking enough water is key for healthy hematocrit levels and overall health. A study in the Journal of Hematology found, “Good hydration is vital for normal hematocrit levels and avoiding dehydration problems.”

In summary, many factors can affect hematocrit levels. Knowing these and making smart choices can help keep hematocrit levels healthy and improve overall well-being.

Symptoms Associated with High Hematocrit

It’s important for patients and doctors to know the symptoms of high hematocrit. High hematocrit means there’s too much red blood cells. This can cause many health problems that need quick attention.

Early Warning Signs

The first signs of high hematocrit can be hard to spot. But knowing the early signs is key. Look out for:

  • Headaches
  • Dizziness or lightheadedness
  • Fatigue or weakness
  • Shortness of breath

These signs might mean there’s a bigger problem that needs a doctor’s help.

Advanced Symptoms of Elevated Hematocrit

As high hematocrit gets worse, symptoms can get more serious. Watch for:

  • Blurred vision or double vision
  • Chest pain or palpitations
  • Itching, mainly after bathing
  • Pain or swelling in the hands and feet

Seeing these signs means you might have a serious issue.

When Symptoms Require Immediate Medical Attention

Some symptoms need you to see a doctor right away. If you have:

  • Severe headache or confusion
  • Chest pain or trouble breathing
  • Severe dizziness or fainting
  • Weakness or numbness on one side of the body

Here’s a table that shows the symptoms of high hematocrit and what they might mean:

Symptom CategorySpecific SymptomsPotential Implications
Early Warning SignsHeadaches, dizziness, fatigueMay indicate early stages of high hematocrit
Advanced SymptomsBlurred vision, chest pain, itchingCan signify progression of the condition
Emergency SymptomsSevere headache, chest pain, severe dizzinessRequire immediate medical attention

Diagnosing High Hematocrit

Diagnosing high hematocrit starts with blood tests and might lead to more detailed tests. We’ll show you how to find out if your hematocrit is too high.

Initial Blood Tests

The first step is a Complete Blood Count (CBC). It checks red blood cells, hemoglobin, and hematocrit. A CBC is key to spotting blood cell count issues.

Here’s what a CBC looks at:

ParameterDescriptionNormal Range
Hematocrit (Hct)Percentage of red blood cells in blood40-54% (men), 37-48% (women)
Hemoglobin (Hb)Protein in red blood cells that carries oxygen13.8-17.2 g/dL (men), 12.1-15.1 g/dL (women)
Red Blood Cell Count (RBC)Number of red blood cells in the blood4.32-5.72 million cells/μL (men), 3.90-5.03 million cells/μL (women)

Follow-up Diagnostic Procedures

If the CBC shows high hematocrit, more tests are needed. These tests may include:

  • Erythropoietin level tests to check for red blood cell production issues
  • Arterial blood gas analysis to check blood oxygen levels
  • Tests for conditions like polycythemia vera or other myeloproliferative disorders

As one expert says, “Finding the cause of high hematocrit needs a detailed look at the patient’s history, physical exam, and lab results.”

“Diagnosing polycythemia vera, for example, needs clinical criteria and molecular testing, like the JAK2 mutation.”

Source: American Society of Hematology

Differential Diagnosis Considerations

When dealing with high hematocrit, it’s important to look at possible causes and rule out similar conditions. Differential diagnosis helps tell the difference between primary and secondary causes of high hematocrit.

Dehydration, chronic hypoxia, and myeloproliferative neoplasms are factors to consider. A detailed diagnostic process helps find the real cause and the right treatment.

Relationship Between Hematocrit and Other Blood Values

Hematocrit is closely tied to other blood components. Together, they give a full picture of health. Knowing these connections is key for correct diagnosis and treatment.

Hemoglobin and Hematocrit Correlation

Hemoglobin and hematocrit are related but different. Hemoglobin is a protein in red blood cells that carries oxygen. Hematocrit shows the red blood cell percentage in blood. Usually, when hematocrit is high, so is hemoglobin.

But, sometimes they don’t match. This can give clues about health issues. For example, high hematocrit with normal or low hemoglobin might mean dehydration or other problems.

“The link between hemoglobin and hematocrit is key in blood tests,” say experts. “Knowing this helps doctors spot health problems.”

Red Blood Cell Count and Hematocrit

The red blood cell count (RBC count) and hematocrit are connected. Hematocrit shows the blood volume taken up by red blood cells. RBC count shows how many red blood cells are in the blood.

A high RBC count can raise hematocrit. But, red blood cell size also plays a role. For example, smaller cells can raise RBC count without raising hematocrit.

Impact on Other Hematological Parameters

High hematocrit can affect other blood values. It can change blood viscosity, which might harm blood flow and heart health. It can also change the erythrocyte sedimentation rate (ESR), a sign of inflammation.

Understanding these connections is important for accurate blood test results. It helps doctors make better decisions for patients.

Managing hematocrit and related blood values needs a detailed approach. This considers the balance between different blood indices. Healthcare providers can then offer treatments that really help patients.

Temporary vs. Chronic Elevations in Hematocrit

It’s important to know the difference between temporary and chronic high hematocrit levels. Hematocrit is the part of blood made up of red blood cells. Various factors can cause it to rise, leading to either short-term or long-lasting changes.

Acute Causes of High Hematocrit

Short-term high hematocrit can come from dehydration, which makes the blood more concentrated. Other quick causes include severe burns, some medicines, and hard exercise. These usually cause a quick rise in hematocrit that goes back to normal once the problem is fixed.

For example, dehydration can make hematocrit go up because there’s less plasma. Drinking water usually fixes this. People who do a lot of exercise might also see a quick rise in hematocrit due to dehydration and more red blood cells from the exercise.

Chronic Conditions Leading to Elevated Hematocrit

Long-term high hematocrit often points to serious health issues. Polycythemia vera, a blood disorder, is a main reason for this. Other long-term problems include COPD, heart disease, and some kidney issues that make more red blood cells.

Living at high altitudes or having chronic lung diseases can also cause long-term high hematocrit. The body makes more red blood cells to handle less oxygen, raising hematocrit levels.

ConditionEffect on HematocritDuration
DehydrationTemporary IncreaseShort-term
Polycythemia VeraChronic IncreaseLong-term
Chronic Lung DiseaseChronic IncreaseLong-term
Severe BurnsTemporary IncreaseShort-term

Distinguishing Between Temporary and Persistent Elevations

Telling apart short-term and long-term high hematocrit is key for right treatment. A detailed medical history, physical check-up, and tests help find the cause. For short-term rises, fixing the cause, like drinking water, is important. For long-term rises, treating the underlying issue, like polycythemia vera or COPD, is needed.

Watching hematocrit levels over time helps tell if it’s short-term or long-term. Long-term high levels that don’t go away with treatment might mean a chronic condition that needs ongoing care.

Health Risks of Untreated High Hematocrit

Untreated high hematocrit poses many risks. It can cause serious problems in the body. These issues affect different systems over time.

Blood Clotting and Thrombosis Risk

High hematocrit increases blood clotting and thrombosis risk. The blood gets thicker and more likely to clot. This can cause deep vein thrombosis (DVT) or stroke.

  • Increased viscosity of blood due to high red blood cell concentration
  • Higher risk of forming blood clots
  • Potential for clots to cause strokes or other cardiovascular events

Cardiovascular Complications

High hematocrit can harm the heart and blood vessels. The heart works harder to pump thick blood. This can lead to high blood pressure and heart failure.

Key cardiovascular risks include:

  1. Hypertension due to increased blood viscosity
  2. Heart failure from prolonged strain on the heart
  3. Increased risk of heart attacks and strokes

Impact on Organ Function

High hematocrit affects organ function. Thick blood reduces blood flow to organs. This can damage organs over time.

For example, it can harm the kidneys and brain. Reduced blood flow to the kidneys can impair their function. Decreased flow to the brain can cause cognitive problems.

Long-term Health Consequences

Untreated high hematocrit can cause long-term health issues. These can include heart disease, kidney disease, and an increased cancer risk.

Understanding these risks is key to managing high hematocrit. It helps prevent long-term damage to the body.

Medical Treatment Options for High Hematocrit

Treating high hematocrit involves several steps to lower risks. We will look at the different medical treatments available.

Phlebotomy (Therapeutic Blood Removal)

Phlebotomy, or blood removal, is a common treatment for high hematocrit. It involves taking blood out to lower red blood cell levels.

“Phlebotomy is a straightforward and effective method to quickly lower hematocrit levels,”

explains a hematology expert. By taking out some red blood cells, phlebotomy makes blood less thick. This reduces the risk of blood clots and heart problems.

Medications to Reduce Red Blood Cell Production

Medications can also help reduce red blood cell production. These are useful for people with polycythemia vera, where too many red blood cells are made. These meds help control red blood cell levels and lower risks.

Treating Underlying Conditions

It’s important to treat the cause of high hematocrit. This might mean fixing dehydration, lung disease, or heart disease. For example, drinking more water can help dilute the blood and lower hematocrit.

Monitoring Treatment Effectiveness

It’s key to check if treatment is working. Regular blood tests are done to see how treatment is going and make changes if needed.

“Regular monitoring is key to avoid over- or under-treatment,”

notes a medical expert. This ongoing check helps make sure treatment is right and keeps side effects down.

With a full treatment plan, people with high hematocrit can manage their condition well. This reduces the chance of health problems.

Lifestyle Changes to Lower Hematocrit Levels

Lifestyle greatly affects hematocrit levels and health. Making smart daily choices can lower hematocrit levels. We’ll look at key areas for adjustments.

Hydration Strategies

Drinking enough water is key for healthy hematocrit levels. Dehydration can make blood thicker. It’s important to drink plenty of water.

Drink at least 8-10 glasses of water daily. Adjust based on your needs, climate, and activity level.

Dietary Modifications

Eating right can help manage hematocrit levels. Some foods can make blood thinner or reduce red blood cells.

  • Eat more omega-3 fatty acids from fish like salmon
  • Add foods rich in antioxidants like berries and leafy greens
  • Watch iron intake to avoid too much

Exercise Considerations

Exercise is important, but the type matters. Choose moderate exercise.

Exercise TypeImpact on Hematocrit
AerobicsModerate impact
High-Intensity TrainingPotential for increase
Yoga and StretchingLow impact

Avoiding Triggering Factors

Some things can raise hematocrit levels. Knowing and avoiding these can help manage levels.

Smoking and high altitudes can affect hematocrit. Avoid smoking and be careful with altitude.

When to Seek Medical Attention for High Hematocrit

It’s important to know when to seek medical help for high hematocrit. High levels can cause serious health problems if not treated. We’ll show you the signs that mean you need to see a doctor right away.

Emergency Warning Signs

Some symptoms mean you need to get medical help fast if your hematocrit is high. These include:

  • Severe headache that doesn’t get better with medicine
  • Dizziness or fainting spells
  • Chest pain or trouble breathing
  • Weakness or numbness in the face, arm, or leg
  • Confusion or trouble speaking

If you have any of these symptoms, seek medical help immediately.

Monitoring Recommendations

It’s key to keep an eye on your hematocrit levels and health. We suggest:

  1. Getting regular blood tests to check your hematocrit and other blood values
  2. Watching for dehydration signs and keeping your fluids balanced
  3. Keeping a symptom journal and telling your doctor about any changes

Your doctor might change these suggestions based on your health and situation.

Questions to Ask Your Healthcare Provider

Being ready for your doctor visits can help your care. Think about asking these questions:

QuestionPurpose
What are the underlying causes of my high hematocrit?Understanding the root cause of your condition
What are the possible complications if it’s not treated?Learning about the risks of high hematocrit
What treatment options are there for my condition?Exploring treatments and management plans

Asking these questions can help you understand your condition better and what steps to take.

Special Considerations for Athletes with High Hematocrit

High hematocrit in athletes can be both a natural adaptation and a sign of health risks. It’s key to know the difference between natural and artificial elevation. We must also consider the impact on sports performance and health, and the ethics in sports.

Natural vs. Artificial Elevation

Athletes might have high hematocrit levels naturally or artificially. Natural causes include genetic predispositions or high-altitude training. Artificial causes include using substances like erythropoietin (EPO). Distinguishing between these causes is vital for fair play and athlete health.

“The use of EPO and other blood doping methods can significantly increase the risk of thrombosis and cardiovascular complications,” experts say. This shows why monitoring and regulating hematocrit levels in athletes is so important.

Sports Performance and Health Implications

A high hematocrit can improve oxygen delivery to muscles, boosting endurance. But, it also makes blood thicker, which can strain the heart and increase clotting risk.

  • Increased oxygen-carrying capacity
  • Enhanced endurance performance
  • Potential cardiovascular risks
  • Increased risk of dehydration if not properly managed

We need to weigh the benefits against the health risks. We must ensure athletes don’t risk their health for a competitive edge.

Ethical and Health Considerations in Sports

The ethics of high hematocrit in athletes are significant. Ensuring fair play while protecting athlete health is a complex challenge. Sports organizations must have strict testing and monitoring to catch and prevent doping.

The World Anti-Doping Agency says, “clean sport is about more than just following the rules “ it’s about protecting the health and rights of athletes.” This highlights the need for a holistic approach to managing hematocrit levels in athletes.

Understanding high hematocrit’s causes and implications helps us support athletes. We can help them reach their goals while keeping their health safe.

High Hematocrit in Specific Populations

It’s important to know how high hematocrit affects different groups. This knowledge helps in diagnosing and treating patients better. Each group has its own needs, so a tailored approach is key.

Children and Adolescents

In young people, high hematocrit can stem from dehydration, heart issues, or high altitudes. It’s vital to look at these factors when checking hematocrit levels. Adjusting for these can help manage high hematocrit well.

Pregnant Women

Pregnancy changes blood volume, which can raise hematocrit levels. Gestational polycythemia is a condition that can affect both mother and baby. We must watch hematocrit levels closely during pregnancy to keep everyone healthy.

Elderly Patients

Elderly people often have health issues like COPD or heart failure that can raise hematocrit. Dealing with high hematocrit in the elderly requires a full care plan. Comprehensive care is essential for elderly patients with high hematocrit.

Patients with Chronic Diseases

People with chronic diseases, like kidney or cancer, may see hematocrit changes. For example, some cancer treatments can boost red blood cell production. We must adjust our approach to managing high hematocrit based on the disease and treatment.

Understanding each group’s unique needs helps healthcare providers create better strategies for managing high hematocrit. This leads to better health outcomes for all.

Conclusion

Knowing about high hematocrit is key to staying healthy. High levels can come from dehydration, polycythemia vera, and other factors. It’s important to notice symptoms early and get medical help fast to avoid problems.

To handle high hematocrit, you need both medical care and changes in your daily life. Fixing the cause and staying hydrated, eating right, and avoiding certain things can help. This way, you can lower the risks of high hematocrit.

Dealing with high hematocrit in a full way helps your blood health and overall health too. It’s critical to work with your doctor to keep an eye on your hematocrit. This ensures you stay healthy and well.

FAQ

What is hematocrit, and why is it important in blood tests?

Hematocrit is the part of blood made up of red blood cells. It’s key in blood tests. It helps find and track health issues like anemia and blood disorders.

What constitutes elevated hematocrit levels?

Levels above 45% for women and 52% for men are usually high. But, normal ranges can vary. High levels might mean dehydration or other health problems.

What are the common causes of high hematocrit?

Causes include dehydration and polycythemia vera. Lung and heart issues, genetics, high altitudes, smoking, and some meds also play a part. Knowing these causes helps in treatment.

How do environmental and lifestyle factors affect hematocrit levels?

Living high, smoking, certain meds, and dehydration can raise hematocrit. Knowing these can help manage high levels.

What are the symptoms associated with high hematocrit?

Symptoms range from headaches and dizziness to chest pain and vision problems. Spotting these signs early is key to getting help.

How is high hematocrit diagnosed?

First, blood tests measure hematocrit levels. Then, more tests find the cause. It’s important to figure out the exact cause.

What is the relationship between hematocrit and other blood values?

Hematocrit is linked to hemoglobin and red blood cell count. High levels can affect other blood values. Understanding these connections is key to diagnosis and treatment.

What are the health risks associated with untreated high hematocrit?

Untreated high hematocrit can cause blood clots and heart problems. It can also harm organ function. Timely treatment is vital to avoid serious issues.

What are the medical treatment options for high hematocrit?

Treatments include phlebotomy and meds to lower red blood cell count. Treating the cause is also important. Keeping an eye on treatment success is essential.

How can lifestyle changes help lower hematocrit levels?

Changes like staying hydrated and eating right can help. Exercise and avoiding triggers are also important. These steps can support medical treatment.

When should one seek medical attention for high hematocrit?

Seek help if symptoms get worse or if there are emergency signs. Regular check-ups and following doctor advice are also important.

Are there special considerations for athletes with high hematocrit?

Yes, athletes need to know about natural and artificial hematocrit increases. They should understand how it affects sports and health. Ethical sports issues also need consideration.

How does high hematocrit affect specific populations?

High hematocrit can mean different things for kids, pregnant women, the elderly, and those with chronic diseases. Tailored care is important for these groups.

References

Kishimoto, S., et al. (2020). Hematocrit, hemoglobin and red blood cells are associated with vascular function and structure: A study of 807 men. Scientific Reports, 10, Article 11543. https://www.nature.com/articles/s41598-020-68319-1

Musallam, K. M., et al. (2012). Elevated hematocrit concentration and the risk of mortality and venous thrombosis following major surgery. Blood, 120(15), 3031-3037. https://www.sciencedirect.com/science/article/pii/S0006497118547728

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