Hypothesis: Histamine issues caused by coagulation defect

In a correspondence today a reader wrote:

Conditions That Release Histamine
 1. Tissue injury: Any physical or chemical agent that injures tissue, skin or mucosa are particularly sensitive to injury and will cause the immediate release of histamine from mast cells. 
2. Allergic reactions: exposure of an antigen to a previously sensitized (exposed) subject can immediately trigger allergic reactions. If sensitized by IgE antibodies attached to their surface membranes will degranulate when exposed to the appropriate antigen and release histamine, ATP and other mediators. 
3. Drugs and other foreign compounds: morphine, dextran, antimalarial drugs, dyes, antibiotic bases, alkaloids, amides, quaternary ammonium compounds, enzymes (phospholipase C). Penicillins, Tetracyclines, Basic drugs- amides, amidines, diamidines, Toxins, venoms, Proteolytic enzymes, Bradykinin, Kallidin, & Substance P  [Src]

Missing the bacteria that produce DAO and having the MAO mutation is a major part of [someone] issues.

This triggered some lateral thinking (Edward de Bono fan here). Histamine comes from mast cells. Mast cells contains TWO items:

  • histamines
  • heparin

What it the histamine problem was not the primary effect but the side effect?

Suppose the body is sending out a chemical message for heparin and the histamine effect is just a side effect.

Heparin is something that I am familiar with, as well as mild coagulation defects. Heparin is not a single chemical but a complex mixture of chemicals. It impacts multiple stages of coagulation.

From Coagulation and Anticoagulants

Suppose that the natural heparin produced by the body has a defect. They do – I know from personal experience. I have the prothrombin G20210a-mutation and have been on heparin. The plead from the body for heparin provides the heparin — but it is not a complete heparin. The body keeps asking for heparin…. causing more and more histamine to be released.

The naive approach to test this hypothesis would be to take heparin!

Any Evidence?

The involvement of coagulation factors, such as tissue factor and fibrinogen, in the pathogenesis of asthma has been reported. The finding of platelet activation in asthma also indicates a link between bronchial inflammation and hemostasis. The pathogenesis of mast celldegranulation and CSU was also shown to be associated with the activation of hemostatic factors such as fibrinogen and FXIIa.

Hemostasis in Allergy. [2018]

Chronic spontaneous urticaria (CSU) [HIVES] is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch. Recently, the activation of the blood coagulation cascade has been suggested to be involved in CSU, but the trigger of the coagulation cascade remains unclear.

Chronic spontaneous urticaria and the extrinsic coagulation system. [2018]

Mast cell heparin released upon activation provides negatively charged surfaces for factor XII (FXII) binding and auto-activation. Activated FXII, the initiating serine protease in both the contact and the intrinsic coagulation system, activates factor XI and prekallikrein, respectively. FXII-mediated bradykinin (BK) formation has been proven in the human plasma of anaphylactic patients as well as in experimental models of anaphylaxis.

The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis. [2017]

Has it been tried?

  • ” The inhibitory action of medium molecular weight heparinyl phenylalanine (MHF) on the type I allergic reaction was due to a reduction or delay in histamine release from mast cells. MHF may be a potent anti-allergic agent. ” [2019]
  • ” Chondroitin sulfate and Heparin may inhibit secretion of histamine from rat connective tissue MC, but their effect on human MC remains unknown.  ” [2018]

Bottom Line

This is just a hypothesis. I could not find any paper on testing for inherited coagulation defects of patients with histamine issues. The hypothesis is a feedback loop caused by ‘corrupt heparin’ being produced and the body asking for complete heparin. The over production of histamine is a side effect of this loop.