Rare blood diseases  


Rare blood diseases can cause a cerebral infarction or cerebral hemorrhage and, as a consequence, cause brain injury.

At the same time severe anemia, caused by a (rare) blood disease, can lead to oxygen deficiency in the brain and increase the risk of a cerebral infarction and cognitive complaints.


Table of contents

1 Introduction on blood cells
2 Anemia and its effect on the brain
3 Thrombotic thrombocytopenic purpura (TTP)
4 Myeloproliferative disorders (MPN or myeloproliferative neoplasms)
5 Aplastic anemia (AA/bone marrow depression)
6 Paroxysmal nocturnal hemoglobinuria (PNH)
7 Factor V Leiden
8 Antiphospholipid syndrome (APS)
9 ADA2 deficiency (DADA2)
10 More blood diseases


1 Introduction on blood cells

The blood contains red blood cells, white blood cells and platelets.
The red blood cells (erythrocytes) bring nutrients and oxygen to the body (and therefore also to the brain). They contain the protein hemoglobin (Hb) that can bind oxygen and carbon dioxide. On average, a human has four billion red blood cells per liter of blood, which live for about three months.
To produce red blood cells, the body needs folic acid and vitamin B12.
The white blood cells (leukocytes) protect the body against bacterial infections and other inflammatory reactions. There are hundreds of red blood cells for each white blood cell.
The platelets (thrombocytes) ensure that the blood clots when there is a wound, so that a scab can be formed. If someone has a real blood disorder with a shortage of platelets (thrombocytopenia), heavy bleeding can occur if the blood does not clot. Forms of thrombosis can also develop.


2 Anemia and its effect on the brain

People who suffer from a severe form of anemia have less oxygen in the blood. Oxygen is needed for proper functioning of the brain and the body.

Anemia can cause problems in the brain, especially due to the iron deficiency, especially at the age at which young people are developing, up to about 20 years of age.
In the elderly, an iron deficiency can cause memory problems and difficulty learning new things. Anemia can disrupt the body's immune system and thermoregulation and leads to fatigue.
A severely low hemoglobin (Hb) level in the blood can be a
cause oxygen deficiency in the brain. This means there is a risk of a cerebral infarction.
Too high a hemoglobin level can cause a blood clot that can also cause a cerebral infarction.
The heart has to work harder to deliver the little oxygen to the brain and muscles.
Possible symptoms of anemia:

  • looking pale
  • fatigue, no energy for normal everyday things
  • limp
  • feeling weak
  • dizziness
  • headache
  • feeling cold, lowered body temperature
  • cold hands and feet
  • numbness
  • shortness of breath
  • chestpain
  • abnormal heart rhythm
  • shortness of breath on exertion


Building blocks of hemoglobin

Hemoglobin is made up of four major building blocks: two alpha-globulin chains and two beta-globulin chains. If the alpha globulin piece is missing it is called alpha thalassemia and if the beta globulin piece is missing it is called beta thalassemia.


A typical hereditary form of anemia is beta-thalassemia (β-thalassemia) in which the beta-globulin part is missing from the hemoglobin. Less hemoglobin is produced. The job of hemoglobin is to pick up oxygen from the lungs and deliver it to the organs in the body. In beta thalassemia, the blood cells do not develop properly and the blood cells are broken down too quickly by the body. This disease is also called Mediterranean disease or Mediterranean anemia.


Beta thalassemia is classified into:

  • intermediary: Complaints start in childhood or when one is older. Complaints are usually less serious than with the major form.
  • major: The complaints start in a child from six months old to two years old. Growth is slower. The whites of the eyes and skin may appear yellowish (icterus). Puberty may start later. Over time, abnormalities of the heart, liver, spleen and bones can develop.


More information:




Alpha thalassemia

Also Alpha-thalassemia (α-thalassemia) is a hereditary anemia disease in which  the alpha-globulin part is missing from the hemoglobin.

Alpha thalassemia is classified into:

  • HbH disease. Mild to moderately severe anemia in a child. Spleen and liver may be enlarged. The forehead can have a striking shape. The upper jaw can also be larger.
  • Alpha thalassemia major. There is severe anemia. Even before birth, the child's body may be swollen. There is sometimes an enlarged spleen or liver. There may be abnormalities of the urinary tract, genitals or heart.


More information:



Other shapes:

  • Delta thalassemia trait: 1 defective gene. The delta globulin gene
  • Delta thalassemia major: 2 defective genes. The delta globulin genes
  • E-thalassemia: 1 or 2 defective genes. The beta-globulin genes with abnormal hemoglobin (HBE)
  • Sickle cell beta thalassemia: 1 defective gene. The beta-globulin gene and abnormal hemoglobin (HBS)


3 Thrombotic thrombocytopenic purpura (TTP)


The name Thrombotic thrombocytopenic purpura (TTP) is derived from three words:


  • thrombotic (derived from thrombosis)
  • thrombocytopenic (too low blood platelet count)
  • purpura (point) bleeding that has a blue / purple color

In this rare and serious clotting disease, there is a serious shortage of platelets (thrombocytes) that normally help the blood to clot when there is a wound.

Such a shortage of platelets is called thrombocytopenia.


96% of all people with TTP lack the enzyme ADAMTS13, which breaks down chains of a clotting protein (vWF / Von Willebrand Factor) into smaller pieces.

Without this enzyme, the clotting proteins can form very long strings in the blood vessels.


These strings can cause the platelets to clump together and be lost, causing a shortage of platelets (thrombocytopenia). This shortage of platelets increases the risk of subcutaneous and other bleeding, such as a cerebral hemorrhage.


The clumping of platelets can also cause blood vessels to clog and close, putting a person at risk of a cerebral infarction or a heart attack. The red blood cells can also become damaged, causing anemia. Clots can get stuck anywhere in the body.


The major consequences such as a heart and/or cerebral infarction are known, but a pulmonary embolism can also occur if a clot ends up in the lungs. It is also possible that these clots create a small scar, which, for example, causes shortness of breath.


This makes it a clotting disease with two characteristics:

  • bleeding due to the clotting problem
  • clots that can clog the blood vessels; a form of thrombosis


Possible complaints:

  • (point)bleeds and bruises
  • pallor and anemia
  • tightness, shortness of breath
  • visual complaints (problems with seeing)
  • headache
  • malaise, feeling sick and weak
  • severe fatigue
  • diarrhea
  • confusion
  • difficulty speaking
  • failure symptoms
  • numbness
  • epileptic attacks
  • coma
  • drowsiness, difficulty arousing
  • renal function disorders


Possible consequences:

  • cerebral infarction
  • stroke
  • hemorrhages and infarctions elsewhere in the body
  • pulmonary embolism
  • the consequences of brain injury
  • death


4 Myeloproliferative disorders (MPN or myeloproliferative neoplasms)


In myeloproliferative disorders (MPN or myeloproliferative neoplasms), the bone marrow produces too many red blood cells and white blood cells (platelets).

This can cause the blood to become too thick, possibly causing a (deep venous) thrombosis in the leg or in the heart, which can cause chest pain or sometimes a heart attack.


Sometimes this causes mild neurological symptoms such as headaches, vision problems or dizziness. The blood clots in the brain can cause a cerebral infarction or a TIA.
The conditions that are classified as myeloproliferative disorders are chronic in nature because they slowly worsen as the number of blood cells increases. It is a relatively rare condition.


MPN includes:


5 Aplastic anemia (AA/bone marrow depression)

Aplastic anemia (bone marrow depression) is a rare bone marrow disease in which fewer red and white blood cells and platelets are produced by the bone marrow, which the body needs. Blood cells do not live long, so continuous production of blood cells in the bone marrow is required. If the bone marrow cannot produce enough blood cells, anemia occurs. The cells that are produced are normal.


A hereditary form of aplastic anemia is called
Fanconi anemia (FA). This is a rare and serious condition that causes a life-threatening decrease in white and red blood cells and platelets. People who suffer from this often have abnormalities from an early age.


6 Paroxysmal nocturnal hemoglobinuria (PNH)

Aplastic anemia (AA) (see previous paragraph) can progress to Paroxysmal nocturnal hemoglobinuria (PNH).
PNH is a disease that, under certain conditions and especially at night, breaks down red blood cells (hemolysis). Paroxysmal means that it occurs in attacks.
Red blood cells are broken down at night in a quarter of patients with PNH. The breakdown products of blood appear in the morning urine, which is therefore red/brown or bloody in color (hemoglobinuria).
PNH is caused by an altered gene in the stem cell where blood cells are produced. With PNH there are complaints of fatigue due to anemia. Clumping of platelets can cause clots in the veins of the liver that cause abdominal pain (Budd-Chiari syndrome). Clots in the brain can be a cause a cerebral infarction (CVA/stroke). This makes PNH the cause of brain damage with all its consequences.


Possible complaints of Aplastic anemia (AA):

  • Shortness of breath because the lungs and heart are not supplied with enough red blood cells that can absorb oxygen
  • Fatigue is partly because the muscles and brain do not receive enough oxygen through the few red blood cells in the blood
  • Weakness and dizziness
  • Pale vision (too low number of red blood cells in the blood vessels under the skin)
  • Frequent or serious infections due to low white blood cell counts
  • Increased risk of bleeding due to low platelet counts. This causes bruises and small red spots under the skin (point hemorrhages or petechiae)
  • Bleeding that is difficult to stop due to low platelet numbers


7 Factor V Leiden

Factor V Leiden is one of the hereditary blood clotting diseases. If the blood clots more quickly than in healthy people, the person suffering from this condition is more likely to develop thrombosis and blood clots that get stuck in the blood vessels and disrupt blood flow (an infarction). When this happens in the brain, a cerebral infarction. If a clot breaks loose and ends up in the lungs, it is called a pulmonary embolism.
Of all people with Factor V Leiden, 10% are known to have clots and thrombosis.
There are two types of Factor V Leiden: the mild and the severe form. If someone has the mild form, he or she has a 50% chance of passing the disease on to any children. However, if the partner also suffers from the mild form and they have children, there is a 25% chance of a child having the severe form. There is a 50% chance that the child will inherit the mild form and a 25% chance that the child will be healthy.
1 in 1000 people has the severe form of Factor V Leiden. 30 in 1000 people have the mild form of Factor V Leiden.


8 Antiphospholipid syndrome (APS)

On our website we have a separate page about the autoimmune disease AntiPhospholipid Syndrome (APS). This syndrome increases the risk of blood clotting and therefore the risk of cerebral infarction.

It belongs to the subcategory of cerebral infarctions.
Follow this link to our page on APS.


9 ADA2 deficiency (DADA2)

We discuss the disease ADA2 deficiency because it can cause brain hemorrhages or cerebral infarctions at a very young age, thereby causing brain damage.

The disease ADA2 deficiency involves a deficiency of the enzyme (protein) adenosine deaminase 2. Gene abnormalities have been found on the ADA2 gene.

Blood vessel inflammation (vasculitis) can occur in the tissues that form the blood vessels.

The severity and symptoms vary, but most people with this condition experience symptoms within the first ten years of life.


Possible complaints:

  • fever
  • muscle strain
  • enlarged liver
  • enlarged spleen
  • enlarged lymph nodes
  • kidney disease
  • high bloodpressure
  • skin discolorations (a spotted blood vessel pattern, livedo racemosa/livedo reticularis)
  • recurrent cerebral hemorrhages (can occur in childhood)
  • recurrent cerebral infarctions (can occur in childhood)


Similarities with Sneddon's syndrome?

There are people with Sneddon syndrome who have complaints simular to those of people with ADA2 deficiency, although Sneddon's starts later in life.

Sneddon's disease also involves repeated cerebral infarctions at a relatively young age and there are the typical skin discolorations (livedo). racemosa /livedo reticularis), a spotted blood vessel pattern on the trunk, hands, feet, buttocks and face.

See an image of livedo recamosa below.

10 More blood diseases

More information can be found on the website of the foundation for rare blood diseases. Also check this website about hemofilia.